Mosaic protein and nucleic acid vaccines against hepatitis C virus

ABSTRACT

The invention relates to immunogenic compositions useful as HCV vaccines. Provided are HCV mosaic polypeptide and nucleic acid compositions which provide higher levels of T-cell epitope coverage while minimizing the occurrence of unnatural and rare epitopes compared to natural HCV polypeptides and consensus HCV sequences.

RELATED APPLICATIONS

This patent application claims the benefit of the filing date of U.S. Provisional patent application No. 61/246,857 under 35 U.S.C. 119(e).

STATEMENT AS TO RIGHTS AND INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with government support under Contract No. DE-AC52-06 NA 25396 awarded by the U.S. Department of Energy. The government has certain rights in the invention.

BACKGROUND OF THE INVENTION

The hepatitis C virus (HCV) is now recognized as the major agent of chronic hepatitis and liver disease worldwide. It has been estimated that HCV infects about 400 million people worldwide, corresponding to more than 3% of the world population. In the United States alone, the economic burden resulting from HCV infections is predicted to reach many billions of dollars in direct medical costs. HCV infection results in chronic infection in between 70 and 80% of cases, which often progresses to liver cirrhosis, liver failure and/or hepatocellular carcinoma.

HCV is a small enveloped flavivirus, which contains a positive-stranded RNA genome of about 10 kilobases. The genome has a single uninterrupted ORF that encodes a polyprotein of 3010-3011 amino acids in length. The structural proteins of HCV include a core protein (C), which is highly immunogenic, as well as two envelope proteins (E1 and E2), and four non-structural proteins NS2, NS3, NS-4 and NS5. It is known that the NS3 region of the virus is important for post-translational processing of the polyprotein into individual proteins, and that the NS5 region encodes an RNA-dependant RNA polymerase.

Treatment options for HCV infected individuals have significantly improved in recent years with the availability of two therapeutics, a pegylated interferon-α and the nucleoside analogue ribavirin⁶⁻⁹. By itself, ribavirin has little effect on HCV, but co-administration with interferon increases the sustained response rate by two- to three-fold. For these reasons, combination therapy is now recommended for hepatitis C, and interferon monotherapy is applied only when there are specific reasons not to use ribavirin.

Unfortunately, these therapies are expensive and require sophisticated medical management, factors which put this option out of reach for the vast majority of infected individuals. Accordingly, the development of a prophylactic vaccine to prevent the continued spread of HCV infection remains critical. Despite over 20 years of vaccine research in numerous laboratories around the world, there is still no HCV vaccine available today.

Nevertheless, several findings indicate that immunological control of HCV is possible. In both humans and chimpanzees, spontaneous eradication of HCV can be achieved during acute infection¹⁰⁻¹⁴. In addition, re-infection after initial clearance has been shown to lead to a shorter duration and lower peak viremia in the chimpanzee model¹⁵; this was also correlated with a resurgence of preexisting HCV-specific cytotoxic T-lymphocytes (CTL). Also, injection drug users with ongoing exposure who previously cleared HCV spontaneously were shown to be less likely to develop chronic HCV infection compared to those with no previous infection¹⁶.

Since the isolation of HCV in 1988¹⁷, a number of studies have dissected the roles of different components of protective immunity to HCV¹⁸. While the function of humoral immune responses against HCV antigens in viral clearance and protection against reinfection is controversial, that of cellular immune responses to HCV is better understood. Virus-specific T lymphocytes, along with neutralizing antibodies, are the principal antiviral immune defense in established viral infections. Control of acute viral replication is clearly associated with expansion of CD4+ and CD8+ T cells¹⁸. Whereas CD8⁺ cytotoxic T cells eliminate virus-infected-cells, CD4⁺ T cells are essential for the efficient regulation of the antiviral immune response. CD4⁺ T cells recognize specific antigens as peptides bound to autologous HLA class II molecules. Several observations support an important role of CD4⁺ T cells in the elimination of HCV infection (Tsai et al., 1997, Hepatology 25: 449-458; Diepolder et al., 1995, Lancet 346: 1006-1009; Diepolder et al., 1997, J. Virol. 71: 6011). In a cohort of patients 20 years after exposure to HCV, about 40% of recovered patients had no detectible antibody response, whereas HCV-specific helper and CTL responses persisted¹⁹. HCV-specific neutralizing antibodies were readily detected in patients with chronic infection and impaired virus-specific CD4⁺ T-cell response, but not in patients who cleared infection with robust virus-specific CD4⁺ T-cell response²⁰. Vigorous, multispecific CTL and T-helper immune responses against HCV antigens in early infection correlate with clearance of HCV infection^(10, 13, 21-26) and HCV-specific CTLs can persist for years after infection^(10, 23). Furthermore, recurrence of HCV viremia has been shown to follow the loss of HCV-specific T Helper cell responses¹¹. In chimpanzees serially infected by HCV, recovered animals did not have detectable antibody against the HCV envelope glycoproteins, while rapid control of secondary infection was associated with a strong T-cell proliferative response and expansion of memory CD4+ and CD8+ T cells²⁷⁻²⁹.

Development of an effective HCV vaccine faces strong obstacles, principal among them being the high level of HCV protein sequence diversity³⁰. For vaccines to be effective, responses covering a wide range of variants are required, as single amino acid substitutions can completely abrogate recognition by HLA class I restricted CD8+ cytotoxic and class II restricted CD4+ T-helper cells²⁴.

For HIV-1, a similarly variable virus, there has been strong interest in rational vaccine design, a relatively new discipline that attempts to define optimal vaccine sequences that minimize differences from the circulating strains while maximizing immunogenicity³³. Even though these vaccine constructs are in a sense artificial, HIV-1 experiments showed that artificially created consensus and ancestral envelope proteins retained folding and conformational antibody binding characteristics, and responses to the vaccine showed enhanced B- and T-cell cross-reactivity compared to natural strains^(34, 35).

Recently, a new computational approach to the design of polyvalent vaccine antigens for T-cell based vaccines was developed and applied to HIV-1³². These antigens consist of sets of “mosaic” proteins which are computationally generated recombinants assembled from fragments of natural sequences and selected to be optimal using a genetic algorithm. Mosaic proteins resemble natural proteins, but are optimized to maximize the coverage of potential T-cell epitopes (nonamer peptides) found in natural sequences and to reduce the number of rare or unique 9-mers to avoid vaccine-specific responses. A small set of 3-4 such HIV-1 “mosaic proteins” provided comparable coverage to thousands of separate peptides. Mosaic proteins can be synthesized and expressed and are immunogenic in mice³⁶. When mosaic constructs for HIV-1 were compared to natural strains in DNA vaccines in mice³⁷, the two- or three-mosaic Env sets elicited the optimal CD4 and CD8 responses. These responses were most evident in CD8 T cells; the three-mosaic set elicited responses to an average of eight peptide pools, compared to two pools for a set of three natural Envs, indicating that synthetic mosaic antigens can induce T-cell responses with expanded breadth and may facilitate the development of effective T-cell-based vaccines.

SUMMARY OF THE INVENTION

The invention provides immunogenic compositions useful as HCV vaccines. Provided are HCV mosaic polypeptide and nucleic acid compositions which provide higher levels of T-cell epitope coverage while minimizing the occurrence of unnatural and rare epitopes compared to natural HCV polypeptides and consensus HCV sequences.

In one embodiment, the invention provides a monovalent HCV mosaic vaccine composition, comprising a polypeptide selected from the group consisting (a) the polypeptide of SEQ ID NO: 1 and (b) the polypeptide of SEQ ID NO: 32. In another embodiment, the invention provides a multivalent HCV mosaic vaccine comprising a set of polypeptides selected from the group consisting of (a) the polypeptides of SEQ ID NOS: 2 and 3, (b) the polypeptides of SEQ ID NOS: 4-6, and (c) the polypeptides of SEQ ID NOS: 7-11. A multivalent HCV mosaic vaccine of the invention may also comprising a set of polypeptides selected from the group consisting of (a) the polypeptides of SEQ ID NOS: 33-34, (b) the polypeptides of SEQ ID NOS: 35-37, and (c) the polypeptides of SEQ ID NOS: 38-41. Yet another multivalent HCV mosaic vaccine comprises a set of polypeptides selected from the group consisting of (a) the polypeptides of SEQ ID NOS: 42-44, and (b) the polypeptides of SEQ ID NOS: 45-48.

In another embodiment, a globally-oriented multivalent HCV mosaic vaccine is provided, and comprises the five polypeptides of SEQ ID NOS: 49-53, or the five polypeptides of SEQ ID NOS: 54-58.

In addition to compositions in which mosaic proteins encode all or part of an HCV polyprotein, the invention provides mosaic vaccine compositions in which all or part of the HCV polyprotein is fragmented to present individual HCV proteins.

Nucleic acid molecules encoding HCV mosaic proteins are also provided, and may be used for the generation of the mosaic proteins of the invention, and as nucleic acid based HCV vaccines. In one embodiment, the invention provides a nucleic acid molecule comprising a polynucleotide encoding a polypeptide which has an amino acid sequence selected from the group consisting of SEQ ID NOS: 1-58. In another embodiment, the invention provides a nucleic acid molecule comprising a polynucleotide encoding a distinct HCV protein within an HCV polyprotein mosaic protein which has an amino acid sequence selected from the group consisting of SEQ ID NOS: 1-58.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. HCV phylogeny, prevalence in the world and comparison to HIV-1. (A) HCV genotypes around the world. Shades in the map show the number of infected people in different nations based on the population prevalence of HCV, and the distribution of genotypes in the HCV sequences from 10 geographic regions contained in the Los Alamos HCV database. Sources: HCV prevalence data: Weekly epidemiological record, No. 6, 2002, 77, 41-48. (B) Phylogenetic tree comparison of HCV and HIV, genotypes, groups and subtypes. Trees are based on manually curated representative complete genome sequence alignments for both viruses. The Findmodel tool was used to determine the best substitution model, which was GTR plus Gamma for both datasets. The trees were constructed using this model in PAUP.

FIG. 2. Comparison of HCV vaccine candidates for a genotype 1 optimized vaccine, expressed as coverage of 9-mers in genotype 1 sequences. Exact, 8 of 9 (one-off), and 7 of 9 (two-off) 9-mer coverage of complete genome sequences was calculated and plotted. “k” is the number of sequences in the cocktail. (A) The lower portion of the graph shows 9-mer coverage of 375 genotype 1 sequences by 1- through 4-valent vaccine cocktail strategies. The upper portion of the graph shows number of un-natural (black) and unique (grey) 9-mers present in each vaccine candidate. (B) Within- and between-subtype coverage. The 9-mer coverage was calculated against 143 1a and 229 1b sequences. Mosaics were optimized using the following training sets: (i) only genotype 1a sequences; (ii) only genotype 1b sequences; (iii) genotypes 1a and 1b sequences combined; (iv) genotype 1 sequences (1a, 1b, 1c combined). C) Coverage of genotypes 1a, 1b and 1c by simultaneously and serially optimized mosaics. Each cocktail was tested against genotype 143 1a sequences (1a), 229 genotype 1b sequences (1b) and 3 genotype 1c sequences (1c).

FIG. 3. Comparison of cocktail (and single strain) HCV vaccine candidates for a globally oriented HCV vaccine. Lower portion of the graph: 9-mer coverage of 6 test sets: 375 genotype 1 sequences, 29 genotype 2 sequences, 7 genotype 3 sequences, genotype 11 4 sequences, 3 genotype 5 sequences, and 42 genotype 6 sequences. Upper portion of the graph: number of un-natural and unique 9-mers present in each vaccine candidate.

FIG. 4. Variability and coverage of HCV protein regions. Upper portions of both graphs: mean Shannon entropy at each position. Lower portion of each graph: 9-mer coverage provided by three vaccine candidates. (A) Calculated against 375 genotype 1 sequences. (B) Calculated against 92 sequences of genotypes 2 through 6 combined.

FIG. 5. Coverage of potential vaccines assessed on a large dataset of short sequences. (A) The coverage of the vaccine candidates in FIG. 4 against (i) Okamoto region (positions 8283 to 8609, H77 numbering) sequences taken from the complete genome (“small set”, N=375 for genotype 1, N=92 for genotypes 2-6); and (ii) all unrelated HCV database sequences covering the Okamoto region (“large set”, N=1983 for genotype 1, N=1887 for genotypes 2-6). (B) The number of and genotype distribution of Okamoto region sequences in the HCV database (“large set”), compared to the entire genome (“small set”).

SEQUENCE LISTING

The amino acid sequences listed in the accompanying sequence listing are shown using standard three letter code, as defined in 37 C.F.R. 1.822. The Sequence Listing is submitted as an ASCII text file, created on Jan. 14, 2011, 1.44 MB, which is incorporated by reference herein.

DETAILED DESCRIPTION OF THE INVENTION Definitions

Unless otherwise defined, all terms of art, notations and other scientific terminology used herein are intended to have the meanings commonly understood by those of skill in the art to which this invention pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and/or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a substantial difference over what is generally understood in the art. The techniques and procedures described or referenced herein are generally well understood and commonly employed using conventional methodology by those skilled in the art, such as, for example, the widely utilized molecular cloning methodologies described in Sambrook et al., Molecular Cloning: A Laboratory Manual 3rd. edition (2001) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.; Current Protocols in Molecular Biology (Ausbel et al., eds., John Wiley & Sons, Inc. 2001. As appropriate, procedures involving the use of commercially available kits and reagents are generally carried out in accordance with manufacturer defined protocols and/or parameters unless otherwise noted.

The term “hepatitis C virus” (HCV) refers to an agent causative of Non-A, Non-B Hepatitis (NANBH). The nucleic acid and amino acid sequences of various HCVs are known. The disease caused by HCV is called hepatitis C, formerly called NANBH. The term HCV, as used herein, denotes a viral species of which pathogenic strains cause NANBH, as well as attenuated strains or defective interfering particles derived therefrom. HCV is a member of the viral family flaviviridae. The morphology and composition of Flavivirus particles are known, and are discussed in Reed et al., Curr. Stud. Hematol. Blood Transfus. (1998), 62:1-37; HEPATITIS C VIRUSES IN FIELDS VIROLOGY (B. N. Fields, D. M. Knipe, P. M. Howley, eds.; 3d ed., 1996). It has recently been found that portions of the HCV genome are also homologous to pestiviruses. Morphologically, Flaviviruses contain a central nucleocapsid surrounded by a lipid bilayer. HCV virions are spherical and have a diameter of about 40-50 nm, with the core element being 25-30 nm in diameter. Along the outer surface of the virion envelope are projections that are about 5-10 nm long with terminal knobs about 2 nm in diameter. The HCV genome is comprised of RNA. It is known that RNA containing viruses have relatively high rates of spontaneous mutation. Therefore, there are multiple HCV strains and isolates of divergent sequences, which can be virulent or a virulent, within the HCV class or species.

An “HCV protein” or “HCV polypeptide” is a polypeptide derived from an HCV. The polypeptide need not be physically derived from HCV, but may be synthetically or recombinantly produced. Moreover, the polypeptide may be derived from any of the various HCV strains, such as from HCV strains 1, 2, 3, 4, 5 or 6. A number of conserved and variable regions are known between these strains and, in general, the amino acid sequences of epitopes derived from these regions will have a high degree of sequence homology.

A polypeptide or protein “fragment” refers to a polypeptide consisting of only a part of the intact full-length polypeptide sequence and structure. The fragment may include a C-terminal deletion and/or an N-terminal deletion of the native or other progenitor polypeptide.

A “polyvalent” HCV mosaic protein or vaccine composition refers to a set of mosaic proteins or polypeptides, whereas a “monovalent” HCV mosaic protein or vaccine refers to a single mosaic protein or polypeptide. A “mosaic vaccine” comprises one or more mosaic proteins or polypeptides. The terms “mosaic polypeptide”, and “mosaic protein” refer to polypeptides and combinations of such polypeptides, wherein the polypeptides are assembled/generated from fragments of natural sequences using a genetic algorithm. In the practice of the method of the invention, mosaic vaccine sequences may be computationally derived using the methods of Fischer et al., 2007, Nature Medicine 13(1): 100-106. Mosaic HCV proteins resemble natural HCV proteins, but are optimized in order to maximize coverage of potential T-cell epitopes found in natural sequences and reduce the presence of rare 9-mers which enables broader immune response.

An “immunological response” to an HCV mosaic protein or vaccine composition (including both polypeptide and polynucleotides encoding polypeptides that are expressed in vivo) or composition is the development in a subject of a humoral and/or a cellular immune response to molecules present in the composition of interest. For purposes of the present invention, a “humoral immune response” refers to an immune response mediated by antibody molecules, while a “cellular immune response” is one mediated by T-lymphocytes and/or other white blood cells. One important aspect of cellular immunity involves an antigen-specific response by cytolytic T-cells (“CTLs”). CTLs have specificity for peptide antigens that are presented in association with proteins encoded by the major histocompatibility complex (SMC) and expressed on the surfaces of cells. CTLs help induce and promote the intracellular destruction of intracellular microbes, or the lysis of cells infected with such microbes. Another aspect of cellular immunity involves an antigen-specific response by helper T-cells. Helper T-cells act to help stimulate the function, and focus the activity of, nonspecific effector cells against cells displaying peptide antigens in association with MHC molecules on their surface. A “cellular immune response” also refers to the production of cytokines, chemokines and other such molecules produced by activated T-cells and/or other white blood cells, including those derived from CD4+ and CD8+ T-cells. A vaccine composition that elicits a cellular immune response may serve to sensitize a vertebrate subject by the presentation of antigen in association with MHC molecules at the cell surface. The cell-mediated immune response is directed at, or near, cells presenting antigen at their surface. In addition, antigen-specific T-lymphocytes can be generated to allow for the future protection of an immunized host.

The term “nucleic acid immunization” refers to the introduction of a nucleic acid molecule encoding one or more selected antigens into a host cell, for the in vivo expression of the antigen or antigens. The nucleic acid molecule can be introduced directly into the recipient subject, such as by injection, inhalation, oral, intranasal and mucosal administration, or the like, or can be introduced ex vivo, into cells which have been removed from the host. In the latter case, the transformed cells are reintroduced into the subject so that an immune response can be mounted against the antigen encoded by the nucleic acid molecule.

The term “nucleic acid” refers to deoxyribonucleotides or ribonucleotides and polymers thereof (“polynucleotides”) in either single- or double-stranded form. Unless specifically limited, the term “polynucleotide” encompasses nucleic acids containing known analogues of natural nucleotides which have similar binding properties as the reference nucleic acid and are metabolized in a manner similar to naturally occurring nucleotides. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively modified variants thereof (e.g. degenerate codon substitutions) and complementary sequences and as well as the sequence explicitly indicated. Specifically, degenerate codon substitutions may be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed-base and/or deoxyinosine residues (Batzer et al., 1991, Nucleic Acid Res. 19: 5081; Ohtsuka et al., 1985 J. Biol. Chem. 260: 2605-2608; and Cassol et al., 1992; Rossolini et al., 1994, Mol. Cell. Probes 8: 91-98). The term nucleic acid is used interchangeably with gene, cDNA, and mRNA encoded by a gene.

The terms “polypeptide,” “peptide” and “protein” are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymers.

The term “amino acid” refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, γ-carboxyglutamate, and O-phosphoserine. Amino acid analogs refers to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., an α carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that functions in a manner similar to a naturally occurring amino acid.

Amino acids may be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, may be referred to by their commonly accepted single-letter codes.

The term “conservatively modified variants” applies to both amino acid and nucleic acid sequences. With respect to particular nucleic acid sequences, conservatively modified variants refers to those nucleic acids which encode identical or essentially identical amino acid sequences, or where the nucleic acid does not encode an amino acid sequence, to essentially identical sequences. Because of the degeneracy of the genetic code, a large number of functionally identical nucleic acids encode any given protein. For instance, the codons GCA, GCC, GCG and GCU all encode the amino acid alanine. Thus, at every position where an alanine is specified by a codon, the codon can be altered to any of the corresponding codons described without altering the encoded polypeptide. Such nucleic acid variations are “silent variations,” which are one species of conservatively modified variations. Every nucleic acid sequence herein which encodes a polypeptide also describes every possible silent variation of the nucleic acid. One of skill will recognize that each codon in a nucleic acid (except AUG, which is ordinarily the only codon for methionine, and TGG, which is ordinarily the only codon for tryptophan) can be modified to yield a functionally identical molecule. Accordingly, each silent variation of a nucleic acid which encodes a polypeptide is implicit in each described sequence.

As to amino acid sequences, one of skill will recognize that individual substitutions, deletions or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters, adds or deletes a single amino acid or a small percentage of amino acids in the encoded sequence is a “conservatively modified variant” where the alteration results in the substitution of an amino acid with a chemically similar amino acid. Conservative substitution tables providing functionally similar amino acids are well known in the art. Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles of the invention.

The following eight groups each contain amino acids that are conservative substitutions for one another: 1) Alanine (A), Glycine (G); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W); 7) Serine (S), Threonine (T); and 8) Cysteine (C), Methionine (M) (see, e.g., Creighton, Proteins (1984)).

Macromolecular structures such as polypeptide structures can be described in terms of various levels of organization. For a general discussion of this organization, see, e.g., Alberts et al., Molecular Biology of the Cell (3^(rd) ed., 1994) and Cantor and Schimmel, Biophysical Chemistry Part I: The Conformation of Biological Macromolecules (1980). “Primary structure” refers to the amino acid sequence of a particular peptide. “Secondary structure” refers to locally ordered, three dimensional structures within a polypeptide. These structures are commonly known as domains. Domains are portions of a polypeptide that form a compact unit of the polypeptide and are typically 25 to approximately 500 amino acids long. Typical domains are made up of sections of lesser organization such as stretches of β-sheet and α-helices. “Tertiary structure” refers to the complete three dimensional structure of a polypeptide monomer. “Quaternary structure” refers to the three dimensional structure formed by the noncovalent association of independent tertiary units. Anisotropic terms are also known as energy terms.

The term “isolated” refers to material which is substantially or essentially free from components which normally accompany the material as it is found in the cellular environment in which it is produced. However, the term “isolated” is not intended refer to the components present in an electrophoretic gel or other separation medium. An isolated component is free from such separation media and in a form ready for use in another application or already in use in the new application/milieu. An “isolated” protein is one that has been identified and separated and/or recovered from a component of its natural environment. Contaminant components of its natural environment are materials that would interfere with therapeutic uses for the protein, and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. In preferred embodiments, an isolated protein is one which is purified (1) to greater than 75% by weight of antibody as determined by the Lowry method, and most preferably more than 99% by weight, (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (3) to homogeneity by SDS-PAGE under reducing or nonreducing conditions using Coomassie blue or, preferably, silver stain.

The term “heterologous” when used with reference to portions of a nucleic acid indicates that the nucleic acid comprises two or more subsequences that are not found in the same relationship to each other in nature. For instance, a nucleic acid is typically recombinantly produced, having two or more sequences from unrelated genes arranged to make a new functional nucleic acid, e.g., a nucleic acid encoding a protein from one source and a nucleic acid encoding a peptide sequence from another source. Similarly, a heterologous protein indicates that the protein comprises two or more subsequences that are not found in the same relationship to each other in nature (e.g., a fusion protein).

The terms “identical” or percent “identity,” in the context of two or more nucleic acids or polypeptide sequences, refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same (i.e., about 70% identity, preferably 75%, 80%, 85%, 90%, or 95% identity over a specified region, when compared and aligned for maximum correspondence over a comparison window, or designated region as measured using a sequence comparison algorithms, or by manual alignment and visual inspection. This definition also refers to the complement of a test sequence, which has substantial sequence or subsequence complementarity when the test sequence has substantial identity to a reference sequence. This definition also refers to the complement of a test sequence, which has substantial sequence or subsequence complementarity when the test sequence has substantial identity to a reference sequence.

When percentage of sequence identity is used in reference to polypeptides, it is recognized that residue positions that are not identical often differ by conservative amino acid substitutions, where amino acids residues are substituted for other amino acid residues with similar chemical properties (e.g., charge or hydrophobicity) and therefore do not change the functional properties of the polypeptide. Where sequences differ in conservative substitutions, the percent sequence identity may be adjusted upwards to correct for the conservative nature of the substitution.

For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. Default program parameters can be used, or alternative parameters can be designated. The sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the program parameters.

A “comparison window”, as used herein, includes reference to a segment of any one of the number of contiguous positions selected from the group consisting of from 20 to 600, usually about 50 to about 200, more usually about 100 to about 150 in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned. Methods of alignment of sequences for comparison are well-known in the art. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, 1981, Adv. Appl. Math. 2:482, by the homology alignment algorithm of Needleman & Wunsch, 1970, J. Mol. Biol. 48:443, by the search for similarity method of Pearson & Lipman, 1988, Proc. Nat'l. Acad. Sci. USA 85:2444, by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by manual alignment and visual inspection (see, e.g., Current Protocols in Molecular Biology (Ausubel et al., eds. 1995 supplement)).

A preferred example of algorithm that is suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al., 1977, Nuc. Acids Res. 25:3389-3402 and Altschul et al., 1990, J. Mol. Biol. 215:403-410, respectively. BLAST and BLAST 2.0 are used, typically with the default parameters described herein, to determine percent sequence identity for the nucleic acids and proteins of the invention. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. This algorithm involves first identifying high scoring sequence pairs (HSPS) by identifying short words of length W in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al., supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPS containing them. The word hits are extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always >0) and N (penalty score for mismatching residues; always <0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a word length (W) of 11, an expectation (E) of 10, M=5, N=−4 and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a word length of 3, and expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 (1989)) alignments (B) of 50, expectation (E) of 10, M=5, N=−4, and a comparison of both strands.

The BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin & Altschul, 1993, Proc. Nat'l. Acad. Sci. USA 90:5873-5787). One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, a nucleic acid is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic acid is less than about 0.2, more preferably less than about 0.01, and most preferably less than about 0.001.

The phrase “stringent hybridization conditions” refers to conditions under which a probe will hybridize to its target subsequence, typically in a complex mixture of nucleic acid, but to no other sequences. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures. An extensive guide to the hybridization of nucleic acids is found in Tijssen, Techniques in Biochemistry and Molecular Biology—Hybridization with Nucleic Probes, “Overview of principles of hybridization and the strategy of nucleic acid assays” (1993). Generally, highly stringent conditions are selected to be about 5-10° C. lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength pH. Low stringency conditions are generally selected to be about 15-30° C. below the Tm. Tm is the temperature (under defined ionic strength, pH, and nucleic concentration) at which 50% of the probes complementary to the target hybridize to the target sequence at equilibrium (as the target sequences are present in excess, at Tm, 50% of the probes are occupied at equilibrium). Stringent conditions will be those in which the salt concentration is less than about 1.0M sodium ion, typically about 0.01 to 1.0M sodium ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30° C. for short probes (e.g., 10 to 50 nucleotides) and at least about 60° C. for long probes (e.g., greater than 50 nucleotides). Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide. For selective or specific hybridization, a positive signal is at least two times background, preferably 10 times background hybridization.

Nucleic acids that do not hybridize to each other under stringent conditions are still substantially identical if the polypeptides which they encode are substantially identical. This occurs, for example, when a copy of a nucleic acid is created using the maximum codon degeneracy permitted by the genetic code. In such cased, the nucleic acids typically hybridize under moderately stringent hybridization conditions.

HCV Mosaic Protein Vaccines

In one aspect, the invention provides HCV mosaic vaccine compositions comprising one or more mosaic proteins. Such HCV mosaic protein vaccines may comprise cocktails of k composite proteins (k being the number of sequence variants in the cocktail), optimized to include the maximum number of potential T-cell epitopes in an input set of viral proteins. The mosaic proteins are generated from natural sequences using genetic algorithms.

Mosaic proteins resemble natural proteins and include the most common forms of potential epitopes. Since CD8+ epitopes are contiguous and typically nine amino-acids long, sets of mosaics can be scored by “coverage” of nonamers (9-mers) in the natural sequences (fragments of similar lengths are also well represented). The HCV mosaic protein design strategy of the invention provides the level of diversity coverage achieved by a massively polyvalent multiple-peptide vaccine, but with important advantages. Vaccine delivery may use intact mosaic proteins or genes. Mosaic proteins exclude low-frequency or unnatural epitopes that are not relevant to circulating strains. Additionally, mosaic proteins resemble native proteins, and may therefore undergo natural processing within the infected cell, in contrast to HCV vaccine designs in which sets of concatenated epitopes are linked (48).

The HCV mosaic vaccines of the invention aim for broader, more globally targeted immunological coverage. In view of applicants determination that immunological coverage diminishes rapidly with increased protein variability in the vaccine composition, preferred HCV mosaic vaccines comprise cocktails of individual mosaics designed the more conservative HCV proteins. For example, as disclosed herein, a three-antigen HCV mosaic vaccine based upon HCV genotype 1 displayed 83% immunological coverage, compared to only 50% coverage displayed by the prototype H77 natural HCV sequence (see Example 1).

The HCV mosaic vaccines of the invention approach near-maximal potential epitope coverage and minimize the number of rare epitopes likely to elicit strain-specific immune responses. For example, the mosaic vaccine approach of the invention proved optimal in terms of providing improved epitope coverage, from just 50% for a an HCV vaccine based upon the natural H77 HCV strain, to 83% with the tetravalent HCV mosaic vaccine described in Example 3. Moreover, the vaccine composition described in Example 3 does not include unnatural or unique epitopes.

An important consideration for any HCV vaccine is its scope. HCV genotype prevalence has geographic associations (Simmonds, 2004, J Gen Virol 85(11): 3173-3188) (FIG. 1A). While genotype 1 is prevalent in Europe and the United States, genotypes 2, 1, 4, 3 and 6 are common in Africa and Asia. Patients with genotype 1 infection have poorer responses to treatment (42, 43). Thus the strong interest in a genotype 1 vaccine (30). A single-genotype vaccine would certainly be useful, and would present fewer design difficulties. Ultimately, however, a vaccine that can provide global protection would obviously be better.

The HIV field faces a similar dilemma, and both single-clade and multi-clade vaccines are being studied, as well as consensus and ancestral sequences, inclusion of only conserved regions, and mosaics (31-33, 44). FIG. 1B compares the genetic variability of HCV and HIV through phylogenetic trees drawn on the same scale. While the overall genetic distances are comparable, HIV-1 vaccine efforts only address the HIV-1 M group, the “main” group in the global pandemic, and not the rare O and N groups. Clearly, a global HIV vaccine needs to cover much less diversity than HCV, underscoring the difficulties for the design of a global vaccine for HCV.

In preferred embodiments of a globally-oriented HCV vaccine, highly variable HCV proteins are not included in the design, in view of observations like the diminished protein coverage generated with NS2 protein (only 38%). Thus, vaccine compositions based upon the more conserved Core, NS3, NS4 and certain parts of NS5 are preferred. In one embodiment, and HCV vaccine of the invention provided more than 75% coverage for all HCV proteins. In other embodiments, more variable protein sequences are included in the vaccine composition when genotype-specific immunization is desired.

The HCV mosaic vaccine design strategies described herein are also useful in generating HCV mosaic vaccine preparations that may provide coverage for all 6 HCV genotypes worldwide. As shown in Examples 20 and 21, pan-genotype, global-coverage HCV mosaic vaccine cocktails provided better coverage than natural or consensus strain vaccines containing the same number of variants, while also possessing the added feature of covering significantly fewer rare epitopes.

In the several Examples which follow, various HCV mosaic protein vaccines, including various multivalent mosaic vaccine cocktails, were generated and evaluated for epitope coverage and the minimization of rare and strain-specific epitopes. Out of 8 single sequence strategies (monovalent mosaic protein), the reference strain H77 (common laboratory HCV strain) provided the worst 9-mer coverage (about 50%) of genotype 1 sequences, and the single mosaic sequence (Example 1) provided the best coverage (about 60%). In addition, the mosaic sequence does not have any unique or unnatural nonamers. The coverage can be significantly improved if more sequences are used. A cocktail of 3 mosaic sequences (Example 3) provides 83% coverage; and, 4 mosaics are slightly better than 3 (Example 4).

Many immunological experiments on genotype 1 use genotype 1a sequences. However, when chimpanzees that had recovered from genotype 1a and 1b infections were challenged with the homologous and heterologous genotype, 36% of heterologous challenges resulted in chronic infections⁴⁵. Similar results were reported in humans^(46,47). In view of the importance of estimating how well mosaic vaccine cocktails would perform outside of the population they were designed for, various HCV mosaic vaccine cocktails optimized for several reference sequence sets were generated and evaluated for epitope coverage and the minimization of rare epitope coverage, as described in the examples sections which follow. These HCV mosaic vaccine cocktails included those optimized against (i) only genotype 1a; (ii) only genotype 1b; (iii) genotypes 1a+1b; and (iv) genotypes 1a+1b+1c (FIG. 2B).

Natural, consensus and mosaic cocktail vaccines designed for one subtype generally provided very poor coverage for other subtypes, illustrating why cross-subtype common re-infection is common even within the same genotype⁴⁵⁻⁴⁷. In contrast, cocktails designed for all of genotype 1 (Examples 1-4) showed dramatically better overall coverage, without reducing within-subtype coverage. For example, the 3-mosaic cocktail designed for all genotype 1 sequences (Example 3) provided >80% coverage of 9-mers from both subtypes 1a and 1b (see FIG. 2B).

In an effort to minimize sampling frequency bias, the invention further provides a serial optimization strategy, which may be employed as described in Examples 17, 18 and 21. The invention's serial optimization strategy is aimed at counteracting the effects of different sampling frequencies. As described further in Examples 17, 18 and 21, this approach succeeds at improving coverage of genotype 1c in the presence of 1a and 1b, as well as improving the coverage of a global HCV vaccine design. While subtype 1c is not common, some of the genotypes with few available sequences are epidemiologically important, and in general, the serial optimization strategy can be used to improve the coverage of under-sampled clades, without significantly diminishing coverage of more common clades. Comparison of tri- or tetravalent cocktails obtained via regular or serial optimization shows that the coverage of subtypes 1a and 1b is stable with serial optimization, while coverage of the rare subtype 1c improves greatly (FIG. 2C).

HCV mosaic proteins and vaccine compositions with relatively low variability have higher intrinsic coverage levels. FIG. 4 illustrates the relation between the Shannon entropy of HCV proteins and their coverage by the H77 reference strain (strategy 1), the 3-mosaic genotype 1 cocktail (strategy 14) and the 5-mosaic global cocktail (strategy 35), for genotype 1 (FIG. 4A) and genotypes 2-6 (FIG. 4B). The HCV Core protein has low variability, and the global cocktail (Example 21) provides 91% coverage. As protein variability increases, the coverage provided by the global vaccine drops to 38% of genotype 1 coverage for the variable NS2 protein (FIG. 4A) and comparable coverage of other genotypes for P7 (FIG. 4B). In contrast, the coverage of genotype 1 provided by a genotype 1 oriented vaccine (Example 3) remains high (more than 75%) for all proteins. This suggests that genotype-specific vaccines might still be effective when based on the more variable proteins.

To explore the potential for mosaic designs to improve the coverage of longer epitopes, the assessment criteria used in the Examples may be changed top calculate coverage of 12-mers in all proteins. This was done with respect to the mosaic vaccine compositions described in Examples 3 and 21, and showed that coverage of 12-mer mosaics was in all cases very similar to that of 9-mers, suggesting that both CTL and T-helper responses may be optimized using the mosaic design strategy.

Preparation of HCV Mosaic Proteins

HCV mosaic proteins may be prepared using various methods well known in the art, including by peptide synthesis and recombinant production means. For example, a mosaic polypeptide may be synthesized according to standard solid-phase methodologies, utilizing the amino acid sequences provided herein, such as may be performed on an Applied Biosystems Model 430A peptide synthesizer (Applied Biosystems, Foster City, Calif.), according to manufacturer's instructions. Other methods of synthesizing peptides or peptidomimetics, either by solid phase methodologies or in liquid phase, are well known to those skilled in the art.

The Mosaic proteins of the invention can be expressed in a variety of host cells, including E. coli, other bacterial hosts, yeast, and various higher eukaryotic cells such as the COS, CHO and HeLa cells lines and myeloma cell lines. The host cells can be mammalian cells, insect cells, or microorganisms, such as, for example, yeast cells, bacterial cells, or fungal cells. HCV mosaic proteins may be expressed intracellularly, or can be secreted from the cell. Intracellular expression often results in high yields. If necessary, the amount of soluble, active fusion polypeptide may be increased by performing refolding procedures (see, e.g., Sambrook et al., supra.; Marston et al., Bio/Technology (1984) 2: 800; Schoner et al., Bio/Technology (1985) 3: 151).

In this regard, there are many expression systems for producing the mosaic proteins of the invention that are well know to those of ordinary skill in the art. (See, e.g., Gene Expression Systems, Fernandes and Hoeffler, Eds. Academic Press, 1999; Russell & Sambrook, supra). Commonly used prokaryotic control sequences, which are defined herein to include promoters for transcription initiation, optionally with an operator, along with ribosome binding site sequences, include such commonly used promoters as the beta-lactamase (penicillinase) and lactose (lac) promoter systems, the tryptophan (trp) promoter, the tac promoter and the lambda-derived P_(L) promoter and N-gene ribosome binding site. The particular promoter system is not critical to the invention, any available promoter that functions in prokaryotes can be used. Standard bacterial expression vectors include plasmids such as pET, pTET, pBR322-based plasmids, e.g., pBLUESCRIPT™, pSKF, pET23D, λ-phage derived vectors, p15A-based vectors and fusion expression systems such as GST. Epitope tags can also be added to recombinant proteins to provide convenient methods of isolation, e.g., c-myc, HA-tag, 6-His tag, maltose binding protein, VSV-G tag, anti-DYKDDDDK tag, or any such tag, a large number of which are well known to those of skill in the art.

For expression of polypeptides in prokaryotic cells other than E. coli, regulatory sequences for transcription and translation that function in the particular prokaryotic species is required. Such promoters can be obtained from genes that have been cloned from the species, or heterologous promoters can be used. For example, the hybrid trp-lac promoter functions in Bacillus in addition to E. coli. These and other suitable bacterial promoters are well known in the art and are described, e.g., in Russell & Sambrook and Ausubel et al. Bacterial expression systems for expressing the proteins of the invention are well known and commercially available.

Similarly, the for expression of polypeptides in eukaryotic cells, transcription and translation sequences that function in the particular eukaryotic species are required. For example, eukaryotic expression systems for mammalian cells, yeast, and insect cells are well known in the art and are also commercially available. In yeast, vectors include Yeast Integrating plasmids (e.g., YIp5) and Yeast Replicating plasmids (the YRp series plasmids) and pGPD-2. Expression vectors containing regulatory elements from eukaryotic viruses are typically used in eukaryotic expression vectors, e.g., SV40 vectors, papilloma virus vectors, and vectors derived from Epstein-Barr virus. Other exemplary eukaryotic vectors include those employing the CMV promoter, metallothionein promoter, murine mammary tumor virus promoter, Rous sarcoma virus promoter, polyhedrin promoter, or other promoters shown effective for expression in eukaryotic cells.

Either constitutive or regulated promoters can be used in the present invention. Regulated promoters can be advantageous because the host cells can be grown to high densities before expression of the polypeptide is induced. High level expression of heterologous proteins slows cell growth in some situations. An inducible promoter is a promoter that directs expression of a gene where the level of expression is alterable by environmental or developmental factors such as, for example, temperature, pH, anaerobic or aerobic conditions, light, transcription factors and chemicals.

Inducible promoters for other organisms are also well known to those of skill in the art. These include, for example, the metallothionein promoter, the heat shock promoter, as well as many others.

Translational coupling may be used to enhance expression as is well known. The strategy uses a short upstream open reading frame derived from a highly expressed gene native to the translational system, which is placed downstream of the promoter, and a ribosome binding site followed after a few amino acid codons by a termination codon. Just prior to the termination codon is a second ribosome binding site, and following the termination codon is a start codon for the initiation of translation. The system dissolves secondary structure in the RNA, allowing for the efficient initiation of translation.

Once expressed, the recombinant polypeptides can be purified according to standard procedures of the art, including ammonium sulfate precipitation, affinity columns, column chromatography, gel electrophoresis and the like (see, generally, R. Scopes, Protein Purification, Springer-Verlag, N.Y. (1982), Deutscher, Methods in Enzymology Vol. 182: Guide to Protein Purification., Academic Press, Inc. N.Y. (1990)).

To facilitate purification of the HCV mosaic proteins of the invention, the nucleic acids that encode the protein can also include a coding sequence for an epitope or “tag” for which an affinity binding reagent is available. Examples of suitable epitopes include the myc and V-5 reporter genes; expression vectors useful for recombinant production of fusion polypeptides having these epitopes are commercially available (e.g., Invitrogen (Carlsbad Calif.) vectors pcDNA3.1/Myc-His and pcDNA3.1/V5-His are suitable for expression in mammalian cells).

Additional expression vectors suitable for attaching a tag to the mosaic proteins of the invention, and corresponding detection systems are known to those of skill in the art, and several are commercially available (e.g., FLAG” (Kodak, Rochester N.Y.). Another example of a suitable tag is a polyhistidine sequence, which is capable of binding to metal chelate affinity ligands. Typically, six adjacent histidines are used, although one can use more or less than six. Suitable metal chelate affinity ligands that can serve as the binding moiety for a polyhistidine tag include nitrilo-tri-acetic acid (NTA) (Hochuli, E. (1990) “Purification of recombinant proteins with metal chelating adsorbents” In Genetic Engineering: Principles and Methods, J. K. Setlow, Ed., Plenum Press, NY; commercially available from Qiagen (Santa Clarita, Calif.)).

Polynucleotides Encoding HCV Mosaic Proteins

The invention further provides nucleic acid molecules comprising a polynucleotide encoding an HCV mosaic protein. Such polynucleotides may be designed from the amino acid sequences of the HCV mosaic proteins provided herein. HCV mosaic protein-encoding polynucleotides are preferably generated by chemical synthesis, but other methods may be used, such as various nucleic acid amplification and targeted mutagenesis strategies, as is well know in the art.

The HCV mosaic protein-encoding polynucleotides and nucleic (acid molecules comprising the same) may be used to generate the mosaic proteins of the invention in recombinant expression systems, as described, supra.

The invention further provides vectors containing polynucleotides encoding the mosaic proteins and polypeptides of the invention, as well as host cells transformed or transfected with, or otherwise made to contain, such vectors. Also provided is a recombinant nucleic acid molecule, which includes at least one polynucleotide encoding an HCV mosaic protein operatively linked to one or more other polynucleotides. The one or more other polynucleotides can be, for example, a transcription regulatory element such as a promoter or polyadenylation signal sequence, or a translation regulatory element such as a ribosome binding site. Such a recombinant nucleic acid molecule can be contained in a vector, which can be an expression vector, and the nucleic acid molecule or the vector can be contained in a host cell. A vector of the invention will generally contain various elements required for replication in a prokaryotic or eukaryotic host system, or both, as required. Such vectors, which include plasmid vectors and viral vectors such as bacteriophage, baculovirus, retrovirus, lentivirus, adenovirus, vaccinia virus, semliki forest virus and adeno-associated virus vectors, are well known and can be purchased from a number of commercial sources or constructed using methods well known in the art.

HCV Mosaic Nucleic Acid Vaccines

In another aspect of the invention, nucleic acid molecules comprising expressible polynucleotides encoding HCV mosaic proteins (expression constructs) may be formulated and utilized as DNA vaccine preparations. Such HCV mosaic DNA vaccines may be used to activate HCV-specific T cells, using standard gene delivery protocols. Methods for gene delivery are known in the art. See, e.g., U.S. Pat. Nos. 5,399,346, 5,580,859, 5,589,466, incorporated by reference herein in their entireties. Genes can be delivered either directly to the vertebrate subject or, alternatively, delivered ex vivo, to cells derived from the subject and the cells reimplanted in the subject. For example, the constructs can be delivered as plasmid DNA, e.g., contained within a plasmid, such as pBR322, pUC, or ColE1.

DNA vaccines may be introduced by a number of different methods, including by injection of DNA in saline, using a standard hypodermic needle. Injection in saline is normally conducted intramuscularly in skeletal muscle, or intradermally, with DNA being delivered to the extracellular spaces. This can be assisted by electroporation, by temporarily damaging muscle fibres with myotoxins such as bupivacaine or by using hypertonic solutions of saline or sucrose. Immune responses to this method of delivery can be affected by many factors, including needle type, needle alignment, speed of injection, volume of injection, muscle type, and age, sex and physiological condition of the individual being injected.

Gene gun delivery ballistically accelerates plasmid DNA (pDNA) that has been adsorbed onto gold or tungsten microparticles into the target cells, using compressed helium as an accelerant. Alternative delivery methods include aerosol instillation of naked DNA on mucosal surfaces, such as the nasal and lung mucosa, and topical administration of pDNA to the eye and vaginal mucosa. Mucosal surface delivery has also been achieved using cationic liposome-DNA preparations, biodegradable microspheres, attenuated Shigella or Listeria vectors for oral administration to the intestinal mucosa, and recombinant adenovirus vectors.

The method of delivery determines the dose of DNA required to raise an effective immune response. Saline injections require variable amounts of DNA, from 10 μg-1 mg, whereas gene gun deliveries require 100 to 1000 times less DNA than intramuscular saline injection to raise an effective immune response. Generally, 0.2 μg-20 μg are required, although quantities as low as 16 ng have been utilized. Saline injections require more DNA because the DNA is delivered to the extracellular spaces of the target tissue (typically, muscle tissue), where physical barriers such as the basal lamina and large amounts of connective tissue must be overcome before it is taken up by the cells, while gene gun deliveries bombard DNA directly into the cells. For a recent review of DNA vaccines, see: Robinson and Pertmer, 2000, DNA vaccines for viral infections, Adv Virus Res 55: 1-74.

HCV mosaic protein expression constructs may be packaged in liposomes prior to delivery to cells. Lipid encapsulation is generally accomplished using liposomes which are able to stably bind or entrap and retain nucleic acid. The ratio of condensed DNA to lipid preparation can vary but will generally be around 1:1 (mg DNA:micromoles lipid), or more of lipid. For a review of the use of liposomes as carriers for delivery of nucleic acids, see, Hug and Sleight, Biochim. Biophys. Acta. (1991) 1097:1-17; Straubinger et al., in Methods of Enzymology (1983), Vol. 101, pp. 512-527.

Liposomal preparations for use with the present invention include cationic (positively charged), anionic (negatively charged) and neutral preparations, with cationic liposomes particularly preferred. Cationic liposomes are readily available. For example, N[1-2,3-dioleyloxy)propyl]-N,N,N-triethylammonium (DOTMA) liposomes are available under the trademark Lipofectin, from GIBCO BRL, Grand Island, N.Y. (See, also, Feigner et al., Proc. Natl. Acad. Sci. USA (1987) 84:7413-7416). Other commercially available lipids include transfectace (DDAB/DOPE) and DOTAP/DOPE (Boerhinger). Other cationic liposomes can be prepared from readily available materials using techniques well known in the art. See, e.g., Szoka et al., Proc. Natl.

A number of viral based systems have been developed for gene transfer into mammalian cells. For example, retroviruses provide a convenient platform for gene delivery systems, such as murine sarcoma virus, mouse mammary tumor virus, Moloney murine leukemia virus, and Rous sarcoma virus. A selected gene can be inserted into a vector and packaged in retroviral particles using techniques known in the art. The recombinant virus can then be isolated and delivered to cells of the subject either in vivo or ex vivo. A number of retroviral systems have been described.

The HCV mosaic protein expression constructs may also be encapsulated, adsorbed to, or associated with, particulate carriers. Such carriers present multiple copies of a selected molecule to the immune system and promote trapping and retention of molecules in local lymph nodes. The particles can be phagocytosed by macrophages and can enhance antigen presentation through cytokine release. Examples of particulate carriers include those derived from polymethyl methacrylate polymers, as well as microparticles derived from poly(lactides) and poly(lactide-co-glycolides), known as PLG. See, e.g., Jeffery et al., 1993, Pharm. Res. 10:362-368.

Evaluating HCV Mosaic Vaccine Performance

The ability of a particular mosaic protein or vaccine composition to stimulate a cell-mediated immunological response may be determined by a number of assays, such as by lymphoproliferation (lymphocyte activation) assays, CTL cytotoxic cell assays, or by assaying for T-lymphocytes specific for the antigen in a sensitized subject. Such assays are well known in the art (Erickson et al., 1993, J. Immunol. 151:4189-4199; Doe et al., 1994, Eur. J. Immunol. 24:2369-2376). Thus, an immunological response may be one which stimulates the production of CTLs and/or the production or activation of helper T-cells. The antigen of interest may also elicit an antibody-mediated immune response. Hence, an immunological response may include one or more of the following effects: the production of antibodies by B-cells and/or the activation of suppressor T-cells.

Various means for estimating or actually measuring the protective immune response generated by an HCV mosaic vaccine preparation of the invention may be utilized, including without limitation, in silico analytical methods designed to determine the degree of T-cell epitope coverage provided by a particular mosaic protein or combination thereof, and in vivo methods of evaluating the HCV mosaic vaccine preparations of the invention in animal models, including chimpanzees. Recently, a mouse model of HCV infection was described, and may be useful in evaluating the potential efficacy of the HCV mosaic vaccines of the invention (Ploss et al., 2009, Nature 457: 882-886). In the Examples which follow, in silico analysis of 9-mer T-cell epitope coverage within the sequence(s) of single mosaic proteins or multivalent cocktails may be used to determine the likely coverage for all possible 9-mer epitopes.

Epitopes recognized by a T cell receptor on an HCV-activated T cell can be identified by, for example, a Chromium-51 release assay or by a lymphoproliferation assay, as is well known in the art. In a ⁵¹Cr release assay, target cells that display the epitope of interest are prepared by cloning a polynucleotide encoding the epitope into an expression vector and transforming the expression vector into the target cells.

Vaccine Formulations and Administration

The HCV mosaic vaccine polynucleotide and polypeptide compositions described herein may be administered to a subject using any suitable delivery means. Methods of delivering nucleic acids into host cells are discussed above. Further, HCV polynucleotides and/or polypeptides may be administered parenterally, by injection, subcutaneously, intramuscularly, transdermally or transcutaneously. Certain adjuvants, e.g. LTK63, LTR72 or PLG formulations, can be administered intranasally or orally. Additional formulations which are suitable for other modes of administration include suppositories. For suppositories, traditional binders and carriers can include, for example, polyalkylene glycols or triglycerides; such suppositories can be formed from mixtures containing the active ingredient in the range of 0.5% to 10%, preferably 1%-2%. Other oral formulations include such normally employed excipients as, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, and the like. These compositions take the form of solutions, suspensions, tablets, pills, capsules, sustained release formulations or powders and contain 10%-95% of active ingredient, preferably 25%-70%.

The HCV mosaic vaccines of the invention are typically prepared as injectables, either as liquid solutions or suspensions. Solid forms suitable for solution or suspension in liquid prior to injection may also be prepared. Such preparations may also be emulsified, or encapsulated in liposomes. Preferably, the vaccine also comprises a pharmaceutically acceptable carrier, which should not itself induce an immune response. Pharmaceutically acceptable carriers are well known to those in the art, and include without limitation large, slowly metabolized macromolecules, such as proteins, polysaccharides, functionalized sepharose, agarose, cellulose, cellulose beads and the like, polylactic acids, polyglycolic acids, polymeric amino acids such as polyglutamic acid, polylysine, and the like.

The HCV mosaic proteins of the invention may be formulated into the immunogenic compound as neutral or salt forms. Pharmaceutically acceptable salts include the acid addition salts (formed with free amino groups of the peptide) and which are formed with inorganic acids such as, for example, hydrochloric or phosphoric acids, or such organic acids such as acetic, oxalic, tartaric, maleic, and the like. Salts formed with the free carboxyl groups can also be derived from inorganic bases such as, for example, sodium, potassium, ammonium, calcium, or ferric hydroxides, and such organic bases as isopropylamine, trimethylamine, 2-ethylamino ethanol, histidine, procaine, and the like.

Vaccine compositions of the invention may also contain liquids or excipients, such as water, saline, glycerol, dextrose, ethanol, or the like, singly or in combination, as well as substances such as wetting agents, emulsifying agents, or pH buffering agents. Liposomes can also be used as a carrier for a composition of the invention, such liposomes are described above.

Various co-stimulatory molecules may be included in the vaccine preparation or delivery protocol. These molecules may improve immunogen presentation to lymphocytes, and include such proteins as B7-1 or B7-2, and cytokines such as GM-CSF, IL-2, and IL-12. Optionally, adjuvants can also be included in a composition. Various adjuvants may be used, including (1) aluminum salts (alum), such as aluminum hydroxide, aluminum phosphate, aluminum sulfate, etc; (2) oil-in-water emulsion formulations (with or without other specific immunostimulating agents such as muramyl peptides or bacterial cell wall components); (3) saponin adjuvants, or particles generated therefrom such as ISCOMs (immunostimulating complexes); (4) Complete Freund's Adjuvant (CFA) and Incomplete Freund's Adjuvant (IFA); (5) cytokines, such as interleukins (e.g., IL-1, IL-2, IL-4, IL-5, IL-6, IL-7, IL-12, etc.), interferons (e.g., gamma interferon), macrophage colony stimulating factor (M-CSF), tumor necrosis factor (TNF), etc; (6) detoxified mutants of a bacterial ADP-ribosylating toxin such as a cholera toxin (CT), a pertussis toxin (PT), or an E. coli heat-labile toxin (LT); (7) other substances that act as immunostimulating agents to enhance the effectiveness of the composition; and (8) microparticles with adsorbed macromolecules. Various novel adjuvants including toll-like receptor agonists have demonstrated enhanced immunogenicity when applied together with HCV immunogens, and may also be used.

The HCV mosaic vaccine compositions of the invention may be administered in a manner compatible with the dosage formulation, and in such amount as will be prophylactically and/or therapeutically effective. The quantity to be administered, which is generally in the range of 5 micrograms to 250 micrograms of polypeptide per dose, depends on the subject to be treated, capacity of the subject's immune system, and the degree of protection desired. Precise amounts of active ingredient required to be administered may depend on the judgment of the practitioner and can be peculiar to each subject.

Vaccine formulations may be introduced in a single dose schedule, or preferably in a multiple dose schedule. A multiple dose schedule is one in which a primary course of vaccination can be with 1-10 separate doses, followed by other doses given at subsequent time intervals required to maintain and or reinforce the immune response, for example, at 1-4 months for a second dose, and if needed, a subsequent dose(s) after several months.

The course of administration may include polynucleotides and polypeptides, together or sequentially (for example, priming with a polynucleotide composition and boosting with a polypeptide composition). The dosage regimen will also, at least in part, be determined by the need of the individual and be dependent upon the judgment of the practitioner.

EXAMPLES Example 1 HCV Genotype 1 Optimized Mosaic Vaccine

In this Example, a mosaic HCV vaccine comprising a single mosaic polypeptide optimized for HCV genotype 1 is generated and tested.

Materials and Methods

HCV Sequence Data:

Full-length Hepatitis C sequences were accessed from a database of HCV sequences (Los Alamos Natl. Lab., Los Alamos, N. Mex.). A total of 143 genotype 1a sequences, 229 genotype 1b sequences, 3 genotype 1c sequences, 29 genotype 2 sequences, 7 genotype 3 sequences, 11 genotype 4 sequences, 3 genotype 5 sequences, and 42 genotype 6 sequences were included in the analysis. Genotype 7 was not included as only one sequence was available.

Mosaic Vaccine Design and Epitope Coverage:

Coverage assessment methods for comparing vaccine cocktail candidates calculate the number of perfect 9-mer matches between the vaccine cocktail and a population of interest, and, as slightly mismatched epitopes often retain some cross-reactivity, also calculate partial 8/9 and 7/9 matches. A steady-state co-evolutionary algorithm was utilized (Fischer et al., 2007, Nature Medicine 13(1): 100-106). “Steady-state” refers to generating one new candidate solution at a time, rather than a whole new population at once; and “co-evolutionary” refers to simultaneously evolving several distinct populations that work together to form a complete solution. The input is an unaligned set of natural sequences; a candidate solution is a set of k pseudo-natural “mosaic” sequences, each of which is formed by concatenating sections of natural sequences. The fitness criterion is population coverage, defined as the proportion of all 9-amino-acid sequence fragments (potential epitopes) in the input sequences that are found in the cocktail.

To initialize the genetic algorithm, k populations of n initial candidate sequences are generated by 2-point recombination between randomly selected natural sequences. Because the input natural sequences are not aligned, “homologous” crossover is used: crossover points in each sequence are selected by searching for short matching strings in both sequences; strings of c-1=8, were used where a typical epitope length is c=9. This ensures that the recombined sequences resemble natural proteins: the boundaries between sections of sequence derived from different strains are seamless, the local sequences spanning the boundaries are always found in nature, and the is mosaics are prevented from acquiring large insertions/deletions or unnatural combinations of amino acids. Mosaic sequence lengths fall within the distribution of natural sequence lengths as a consequence of mosaic construction: recombination is only allowed at identical regions, reinforced by an explicit software prohibition against excessive lengths to prevent reduplication of repeat regions. (Such “in frame” insertion of reduplicated epitopes could provide another way of increasing coverage without generating unnatural 9-mers, but their inclusion would create “unnatural” proteins.) Initially, the cocktail contains one randomly chosen “winner” from each population. The fitness score for any individual sequence in a population is the coverage value for the cocktail consisting of that sequence plus the current winners from the other populations. The individual fitness of any sequence in a population therefore depends dynamically upon the best sequences found in the other populations.

Optimization proceeds one population at a time. For each iteration, two “parent” sequences are chosen. The first parent is chosen using “2-tournament” selection: two sequences are picked at random from the current population, scored, and the better one is chosen. This selects parents with a probability inversely proportional to their fitness rank within the population, without the need to actually compute the fitness of all individuals. The second parent is chosen in the same way (50% of the time), or is selected at random from the set of natural sequences. 2-point homologous crossover between the parents is then used to generate a “child” sequence. Any child containing a 9-mer that was very rare in the natural population (found less than 3 times) is rejected immediately. Otherwise, the new sequence is scored, and its fitness is compared with the fitnesses of four randomly chosen sequences from the same population. If any of the four randomly chosen sequences has a score lower than that of the new sequence, it is replaced in the population by the new sequence. Whenever a sequence is encountered that yields a better score than the current population “winner”, that sequence becomes the winner for the current population and so is subsequently used in the cocktail to evaluate sequences in other populations. A few such optimization cycles (typically 10) are applied to each population in turn, and this process continues cycling through the populations until evolution stalls (i.e. no improvement has been made for a defined number of generations). At this point, the entire procedure is restarted using newly generated random starting populations, and the restarts are continued until no further improvement is seen.

The algorithm also enables optional inclusion of one or more fixed sequences of interest (for example, a consensus) in the cocktail and will evolve the other elements of the cocktail in order to optimally complement that fixed strain. As these solutions were suboptimal, they are not included here. An additional program selects from the input file the k best natural strains that in combination provide the best population coverage.

Measure of Variability:

Shannon entropy, a diversity measure that incorporates both the number of possible amino acids allowed and their frequency,

$\left( {- {\sum\limits_{aa}{{P_{i}({aa})}{\log_{10}\left( {P_{i}({aa})} \right)}}}} \right.$ where P_(i)(aa) is the proportion of each amino acid in column i of a sequence alignment (Korber et al., 1994, J. Virol. 68(10): 6730-6744; Yusim et al., 2002, J. Virol. 76(17): 8757-8768), was calculated for each position in the protein alignment. Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a single HCV mosaic protein vaccine (k=1) was employed, resulting in the generation of the HCV mosaic protein 8.1 having the amino acid sequences shown in SEQ ID NO: 1 (see Table of Sequences).

Epitope coverage of HCV mosaic vaccine 8.1 was evaluated as to (i) maximum coverage of 9-mers present in genotype 1 sequences (lower graph); (ii) fewest unique and unnatural 9-mers present (upper graph) in comparison to other mosaic sequences and cocktails in FIG. 2A. Exact match coverage of 9-mer epitopes across genotype 1 was about 60%, but nevertheless higher than all natural and consensus genotype 1 sequences evaluated (FIG. 2A).

Example 2 Two-Mosaic HCV Genotype 1 Optimized Vaccine

In this Example, a mosaic HCV vaccine comprising a cocktail of two mosaic polypeptides optimized for HCV genotype 1 were generated and tested. HCV sequences, and design and evaluation methods were as described in Example 1.

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a cocktail of two HCV mosaic proteins (k=2) was employed, resulting in the generation of the HCV mosaic proteins 11.1 and 11.2, having the amino acid sequences shown in SEQ ID NOS: 2 and 3, respectively (see Table of Sequences).

Epitope coverage of the HCV mosaic vaccine cocktail consisting of mosaic proteins 11.1 and 11.2 was evaluated as to (i) maximum coverage of 9-mers present in genotype 1 sequences (lower graph); (ii) fewest unique and unnatural 9-mers present (upper graph) in comparison to other mosaic sequences and cocktails in FIG. 2A. Exact match coverage of 9-mer epitopes across genotype 1 was nearly 80%, higher than the natural and consensus genotype 1 sequences evaluated (FIG. 2A).

Example 3 Three-Mosaic HCV Genotype 1 Optimized Vaccine

In this Example, a mosaic HCV vaccine comprising a cocktail of three mosaic polypeptides optimized for HCV genotype 1 were generated and tested. HCV sequences, and design and evaluation methods were as described in Example 1.

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a cocktail of three HCV mosaic proteins (k=3) was employed, resulting in the generation of the HCV mosaic proteins 14.1, 14.2 and 14.3, having the amino acid sequences shown in SEQ ID NOS: 4-6, respectively (see Table of Sequences).

Epitope coverage of the HCV mosaic vaccine cocktail consisting of these three mosaic proteins was evaluated as to (i) maximum coverage of 9-mers present in genotype 1 sequences (lower graph); (ii) fewest unique and unnatural 9-mers present (upper graph) in comparison to other mosaic sequences and cocktails in FIG. 2A. Exact match coverage of 9-mer epitopes across genotype 1a and 1b subtypes was greater than 80%, higher than the natural and consensus genotype 1 sequences evaluated (FIG. 2A).

Example 4 Four-Mosaic HCV Genotype 1 Optimized Vaccine

In this Example, a mosaic HCV vaccine comprising a cocktail of four mosaic polypeptides optimized for HCV genotype 1 were generated and tested. HCV sequences, and design and evaluation methods were as described in Example 1.

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a cocktail of four HCV mosaic proteins (k=4) was employed, resulting in the generation of the HCV mosaic proteins 16.1, 16.2, 16.3 and 16.4, having the amino acid sequences shown in SEQ ID NOS: 7-11, respectively (see Table of Sequences).

Epitope coverage of the HCV mosaic vaccine cocktail consisting of these three mosaic proteins was evaluated as to (i) maximum coverage of 9-mers present in genotype 1 sequences (lower graph); (ii) fewest unique and unnatural 9-mers present (upper graph) in comparison to other mosaic sequences and cocktails in FIG. 2A. Exact match coverage of 9-mer epitopes across genotype 1a and 1b subtypes was greater than 85%, higher than the best natural genotype 1 sequences compared, and slightly higher that the mosaic protein set of Example 3, supra. (FIG. 2A).

Example 5 Mosaic HCV Genotype 1a Optimized Vaccine

In this Example, a mosaic HCV vaccine comprising a single HCV mosaic polypeptide optimized for HCV genotype 1a was generated and tested for cross-coverage with genotype 1b. HCV sequences, and design and evaluation methods were as described in Example 1.

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a single HCV genotype 1a mosaic protein (k=1) was employed, resulting in the generation of the HCV mosaic protein 17.1, having the amino acid sequence shown in SEQ ID NO: 12 (see Table of Sequences).

Epitope coverage of the HCV mosaic protein 17.1 was evaluated as to (i) maximum coverage of 9-mers present in genotype 1a versus (ii) genotype 1b sequences in comparison to other natural, consensus and mosaic cocktails, as shown in FIG. 2B. Exact match coverage of 9-mer epitopes across genotype 1a approached 80%, but was extremely poor for cross-coverage of genotype 1b (FIG. 2B).

Example 6 Two-Mosaic HCV Genotype 1a Optimized Vaccine

In this Example, a mosaic HCV vaccine comprising a set of two HCV mosaic polypeptides optimized for HCV genotype 1a was generated and tested for cross-coverage with genotype 1b. HCV sequences, and design and evaluation methods were as described in Example 1.

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a two-mosaic HCV genotype 1a vaccine cocktail (k=2) was employed, resulting in the generation of the HCV mosaic proteins 18.1 and 18.2, having the amino acid sequences shown in SEQ ID NOS: 13 and 14, respectively (see Table of Sequences).

Epitope coverage of the HCV mosaic protein cocktail was evaluated as to (i) maximum coverage of 9-mers present in genotype 1a versus (ii) genotype 1b sequences, in comparison to other natural, consensus and mosaic cocktails, as shown in FIG. 2B. Exact match coverage of 9-mer epitopes across genotype 1a exceeded 80%, but was extremely poor for cross-coverage of genotype 1b (FIG. 2B).

Example 7 Three-Mosaic HCV Genotype 1a Optimized Vaccine

In this Example, a mosaic HCV vaccine comprising a set of three HCV mosaic polypeptides optimized for HCV genotype 1a was generated and tested for cross-coverage with genotype 1b. HCV sequences, and design and evaluation methods were as described in Example 1.

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a three-mosaic HCV genotype 1a vaccine cocktail (k=3) was employed, resulting in the generation of the HCV mosaic proteins 19.1, 19.2 and 19.3, and having the amino acid sequences shown in SEQ ID NOS: 15-17, respectively (see Table of Sequences).

Epitope coverage of the HCV mosaic protein cocktail was evaluated as to (i) maximum coverage of 9-mers present in genotype 1a versus (ii) genotype 1b sequences, in comparison to other natural, consensus and mosaic cocktails, as shown in FIG. 2B. Exact match coverage of 9-mer epitopes across genotype 1a approached 90%, but was extremely poor for cross-coverage of genotype 1b (FIG. 2B).

Example 8 Four-Mosaic HCV Genotype 1a Optimized Vaccine

In this Example, a mosaic HCV vaccine comprising a set of four HCV mosaic polypeptides optimized for HCV genotype 1a was generated and tested for cross-coverage with genotype 1b. HCV sequences, and design and evaluation methods were as described in Example 1.

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a four-mosaic HCV genotype 1a vaccine cocktail (k=4) was employed, resulting in the generation of the HCV mosaic proteins 20.1, 20.2, 20.3 and 20.4, having the amino acid sequences shown in SEQ ID NOS: 18-21, respectively (see Table of Sequences).

Epitope coverage of the HCV mosaic protein cocktail was evaluated as to (i) maximum coverage of 9-mers present in genotype 1a versus (ii) genotype 1b sequences, in comparison to other natural, consensus and mosaic cocktails, as shown in FIG. 2B. Exact match coverage of 9-mer epitopes across genotype 1a exceeded 90%, but was relatively poor for cross-coverage of genotype 1b (less than 50%) (FIG. 2B).

Example 9 Mosaic HCV Genotype 1b Optimized Vaccine

In this Example, a mosaic HCV vaccine comprising a single HCV mosaic polypeptide optimized for HCV genotype 1b was generated and tested for cross-coverage with genotype 1a. HCV sequences, and design and evaluation methods were as described in Example 1.

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a single HCV genotype 1b mosaic protein (k=1) was employed, resulting in the generation of the HCV mosaic protein 21.1, having the amino acid sequence shown in SEQ ID NO: 22 (see Table of Sequences).

Epitope coverage of the HCV mosaic protein 21.1 was evaluated as to (i) maximum coverage of 9-mers present in genotype 1b versus (ii) genotype 1a sequences in comparison to other natural, consensus and mosaic cocktails, as shown in FIG. 2B. Exact match coverage of 9-mer epitopes across genotype 1b was about 75%, but was extremely poor for cross-coverage of genotype 1a (FIG. 2B).

Example 10 Two-Mosaic HCV Genotype 1b Optimized Vaccine

In this Example, a mosaic HCV vaccine comprising a set of two HCV mosaic polypeptides optimized for HCV genotype 1b was generated and tested for cross-coverage with genotype 1a. HCV sequences, and design and evaluation methods were as described in Example 1.

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a two-mosaic HCV genotype 1b vaccine cocktail (k=2) was employed, resulting in the generation of the HCV mosaic proteins 22.1 and 22.2, having the amino acid sequences shown in SEQ ID NOS: 23 and 24, respectively (see Table of Sequences).

Epitope coverage of the HCV mosaic protein cocktail was evaluated as to (i) maximum coverage of 9-mers present in genotype 1b versus (ii) genotype 1a sequences, in comparison to other natural, consensus and mosaic cocktails, as shown in FIG. 2B. Exact match coverage of 9-mer epitopes across genotype 1b exceeded 80%, but was extremely poor for cross-coverage of genotype 1a (FIG. 2B).

Example 11 Three-Mosaic HCV Genotype 1b Optimized Vaccine

In this Example, a mosaic HCV vaccine comprising a set of three HCV mosaic polypeptides optimized for HCV genotype 1b was generated and tested for cross-coverage with genotype 1a. HCV sequences, and design and evaluation methods were as described in Example 1.

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a three-mosaic HCV genotype 1b vaccine cocktail (k=3) was employed, resulting in the generation of the HCV mosaic proteins 23.1, 23.2 and 23.3, and having the amino acid sequences shown in SEQ ID NOS: 25-27, respectively (see Table of Sequences).

Epitope coverage of the HCV mosaic protein cocktail was evaluated as to (i) maximum coverage of 9-mers present in genotype 1b versus (ii) genotype 1a sequences, in comparison to other natural, consensus and mosaic cocktails, as shown in FIG. 2B. Exact match coverage of 9-mer epitopes across genotype 1b exceeded 80%, but was extremely poor for cross-coverage of genotype 1a (FIG. 2B).

Example 12 Four-Mosaic HCV Genotype 1b Optimized Vaccine

In this Example, a mosaic HCV vaccine comprising a set of four HCV mosaic polypeptides optimized for HCV genotype 1b was generated and tested for cross-coverage with genotype 1a. HCV sequences, and design and evaluation methods were as described in Example 1.

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a four-mosaic HCV genotype 1a vaccine cocktail (k=4) was employed, resulting in the generation of the HCV mosaic proteins 24.1, 24.2, 24.3 and 24.4, having the amino acid sequences shown in SEQ ID NOS: 28-31, respectively (see Table of Sequences).

Epitope coverage of the HCV mosaic protein cocktail was evaluated as to (i) maximum coverage of 9-mers present in genotype 1b versus (ii) genotype 1a sequences, in comparison to other natural, consensus and mosaic cocktails, as shown in FIG. 2B. Exact match coverage of 9-mer epitopes across genotype 1b was about 85%, but was relatively poor for cross-coverage of genotype 1b (about 50%) (FIG. 2B).

Example 13 Mosaic HCV Genotype 1a/1b Optimized Vaccine

In this Example, a mosaic HCV vaccine comprising a single HCV mosaic polypeptide optimized for HCV genotypes 1a and 1b was generated and tested for coverage of each of the subtypes. HCV sequences, and design and evaluation methods were as described in Example 1.

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a single HCV mosaic protein (k=1) optimized for both genotype 1 subtypes 1a and 1b was employed, resulting in the generation of the HCV mosaic protein 25.1, having the amino acid sequence shown in SEQ ID NO: 32 (see Table of Sequences).

Epitope coverage of the HCV mosaic protein 25.1 was evaluated as to maximum coverage of 9-mers present in both subtypes, in comparison to other mosaics, as shown in FIG. 2B.

Example 14 Two-Mosaic HCV Genotype 1a/1b Optimized Vaccine

In this Example, a mosaic HCV vaccine comprising a set of two HCV mosaic polypeptides optimized for HCV genotypes 1a and 1b was generated and tested for coverage of each of the subtypes. HCV sequences, and design and evaluation methods were as described in Example 1.

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a two-mosaic HCV vaccine cocktail (k=2) optimized for both genotype 1 subtypes 1a and 1b was employed, resulting in the generation of the HCV mosaic proteins 26.1 and 26.2, having the amino acid sequences shown in SEQ ID NOS: 33 and 34, respectively (see Table of Sequences).

Epitope coverage of the HCV mosaic protein cocktail was evaluated as to maximum coverage of 9-mers present in both subtypes, in comparison to other mosaics, as shown in FIG. 2B. Exact match coverage of 9-mer epitopes across genotype 1a exceeded 80%, but was slightly lower for coverage of genotype 1b (FIG. 2B).

Example 15 Three-Mosaic HCV Genotype 1a/1b Optimized Vaccine

In this Example, a mosaic HCV vaccine comprising a set of three HCV mosaic polypeptides optimized for HCV genotypes 1a and 1b was generated and tested for coverage of each of the subtypes. HCV sequences, and design and evaluation methods were as described in Example 1.

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a three-mosaic HCV vaccine cocktail (k=3) optimized for both genotype 1 subtypes 1a and 1b was employed, resulting in the generation of the HCV mosaic proteins 27.1, 27.2 and 27.3, and having the amino acid sequences shown in SEQ ID NOS: 35-37, respectively (see Table of Sequences).

Epitope coverage of the HCV mosaic protein cocktail was evaluated as to maximum coverage of 9-mers present in both subtypes, in comparison to other mosaics, as shown in FIG. 2B. Exact match coverage of 9-mer epitopes across both subtypes was about the same and exceeded 80% (FIG. 2B).

Example 16 Four-Mosaic HCV Genotype 1a/1b Optimized Vaccine

In this Example, a mosaic HCV vaccine comprising a set of four HCV mosaic optimized for HCV genotypes 1a and 1b was generated and tested for coverage of each of the subtypes. HCV sequences, and design and evaluation methods were as described in Example 1.

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a four-mosaic HCV vaccine cocktail (k=4) optimized for both genotype 1 subtypes 1a and 1b was employed, resulting in the generation of the HCV mosaic proteins 28.1, 28.2, 28.3 and 28.4, having the amino acid sequences shown in SEQ ID NOS: 38-41, respectively (see Table of Sequences).

Epitope coverage of the HCV mosaic protein cocktail was evaluated as to maximum coverage of 9-mers present in both subtypes, in comparison to other mosaics, as shown in FIG. 2B. Exact match coverage of 9-mer epitopes across both subtypes was about the same and averaged about 85% (FIG. 2B), representing a significant improvement over the three-mosaic protein combination optimized for both subtypes (see Example 15, supra).

Example 17 Serially-Optimized Three-Mosaic Genotype 1 Vaccine

In this Example, a mosaic HCV vaccine comprising a set of three HCV mosaic polypeptides serially optimized for HCV genotypes 1a, 1b and 1c was generated and tested for cross-coverage with genotypes 1a and 1b.

Materials and Methods:

Since only 3 genotype 1c full genome sequences were available, compared to 104 1b and 69 1a sequences (FIG. 2B), a “serial optimization” protocol was adopted, in which one mosaic was optimized for subtype 1b, then a second mosaic optimized for subtype 1a while taking the presence of the 1b-optimized mosaic in the cocktail into account, then a third mosaic optimized for subtype 1c, taking the presence of both other mosaics in the cocktail into account (FIG. 2C). Analogously, a fourth serially optimized strain was optimized on the whole set of genotype 1 sequences (strategy 30).

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a three-mosaic HCV vaccine cocktail (k=3) optimized for both genotype 1 subtypes 1a, 1b and 1c was employed, resulting in the generation of the HCV mosaic proteins 29.1, 29.2 and 29.3, and having the amino acid sequences shown in SEQ ID NOS: 42-44, respectively (see Table of Sequences).

Epitope coverage of the HCV mosaic protein cocktail was evaluated as to maximum coverage of 9-mers present in both subtypes 1a and 1b, in comparison to other mosaics, as shown in FIG. 2B. Exact match coverage of 9-mer epitopes across both subtypes was about the same and exceeded 80% (FIG. 2B),

Comparison of trivalent mosaic cocktail of this Example, obtained via regular or serial optimization (FIG. 2C), shows that the coverage of subtypes 1a and 1b is stable with serial optimization, while coverage of the rare subtype 1c improves greatly.

Example 18 Serially-Optimized Four-Mosaic Genotype 1 Vaccine

In this Example, a mosaic HCV vaccine comprising a set of four HCV mosaic serially optimized for HCV genotypes 1a, 1b and 1c was generated and tested for cross-coverage with genotypes 1a and 1b.

Materials and Methods:

Serial optimization was conducted as described in Example 17, supra, further including a fourth serially optimized strain which was optimized on the whole set of genotype 1 sequences.

Results:

Mosaic HCV proteins designed to maximize coverage of common 9-mer epitopes while minimizing the inclusion of rare epitopes were generated. In this Example, a strategy for designing a four-mosaic HCV vaccine cocktail (k=4) optimized for both genotype 1 subtypes 1a, 1b and 1c was employed, resulting in the generation of the HCV mosaic proteins 30.1, 30.2, 30.3 and 30.4, having the amino acid sequences shown in SEQ ID NOS: 45-48, respectively (see Table of Sequences).

Epitope coverage of the HCV mosaic protein cocktail was evaluated as to maximum coverage of 9-mers present in both subtypes 1a and 1b, in comparison to other mosaics, as shown in FIG. 2B. Exact match coverage of 9-mer epitopes across both subtypes was about the same and averaged about 85% (FIG. 2B), representing a modest improvement over the three-mosaic protein combination optimized for both subtypes 1a and 1b (see Example 17, supra). These results were similar to those obtained with same-k sets of mosaics optimized for only the prevalent subtypes 1a and 1b (see Examples 15 and 16).

Comparison of tetravalent mosaic cocktail of this Example, obtained via regular or serial optimization (FIG. 2C), shows that the coverage of subtypes 1a and 1b is stable with serial optimization, while coverage of the rare subtype 1c improves greatly.

Example 19 Pentavalent HCV Mosaic for Global HCV Vaccine

In this Example, a mosaic HCV vaccine comprising a set of five HCV mosaic proteins optimized across the global HCV sequence set was generated and tested for cross-coverage of the global set. The coverage of the entire 6-genotype target set provided by two genotype 1 oriented vaccine cocktails and 5 new globally oriented vaccine cocktails is shown in FIG. 3. Design and evaluation methods were as described in Example 1.

A set of mosaic proteins 32.1, 32.2, 32.3, 30.4 and 35.5, having the amino acid sequences shown in SEQ ID NOS: 49-53, respectively (see Table of Sequences), was generated and epitope coverage of the HCV mosaic vaccine cocktail was evaluated as to maximum coverage of 9-mers present in genotypes 1-6, in comparison to other mosaics, as shown in FIG. 3.

The H77 sequence provides 50% coverage of genotype 1 but only 14-24% coverage of genotypes 2 through 6. As expected, a trivalent mosaic cocktail optimized for genotype 1 (see Example 3, supra) improves the coverage of genotype 1, but not of the other genotypes. A consensus of genotype consensuses not only provides low coverage of all genotypes, but also has close to 500 un-natural nonamers (FIG. 3).

Example 20 Serially-Optimized Pentavalent Global HCV Vaccine

As shown in Example 19, supra, the five-mosaic cocktail optimized for a global set of natural strains provides very uneven coverage of all genotypes. This is partly due to a bias towards genotypes with more sequences (genotypes 1, 2 and 6). To overcome this bias, 5 genotype consensus sequences (for each of the five genotypes with more than two sequences available), 5 best natural sequences, and 5 mosaics serially optimized for 5 genotypes, respectively, were generated.

Serial optimization was conducted as described in Example 17, except that the optimization sequences was, first genotype 1, then genotype 6, then genotype 2, then genotype 4, then genotype 3.

The 5 mosaic proteins serially optimized for all five genotypes were generated, and have the sequences of SEQ ID NOS: 54-58. Upon evaluation of global HCV strain coverage, this mosaic vaccine cocktail provides some (2-5%) gain compared to the other two, and it contains no un-natural and lowest number of unique nonamers, suggesting it may be the best candidate for a global vaccine (FIG. 3, right of the dashed line).

Example 20 Evaluation of HCV mosaic vaccine cocktails Coverage of Unsampled Circulating HCV

In this Example, the impact of expanding the sampling set for determining epitope coverage was assessed across the short and heavily-sequenced 80-100AA “Okamoto region” of the NS5B HCV protein, indicating that performance of the vaccines is almost the same when evaluating coverage across the larger set. There is almost 10 times more sequencing information for this region than for the entire HCV genome (FIG. 5B).

The complete-genome coverage of the mosaic vaccine preparations of Examples 3 and 21 (compared to the natural H77 strain) were evaluated for epitope coverage across all Okamoto region sequences in the Los Alamos HCV database (FIG. 5A).

All considered vaccine cocktails covered the Okamoto sequences (N=1983 for genotype 1, N=1887 for genotypes 2-6) almost as well as the much smaller complete genome set, suggesting that although the vaccine designs are based on a limited set of sequences, good coverage of unstapled circulating viruses can be expected. Since the Okamoto region is quite variable, this comparison provides a conservative estimate of a performance of vaccine based on more conserved regions of genome.

All publications, patents, and patent applications cited in this specification are herein incorporated by reference as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference.

The present invention is not to be limited in scope by the embodiments disclosed herein, which are intended as single illustrations of individual aspects of the invention, and any which are functionally equivalent are within the scope of the invention. Various modifications to the models and methods of the invention, in addition to those described herein, will become apparent to those skilled in the art from the foregoing description and teachings, and are similarly intended to fall within the scope of the invention. Such modifications or other embodiments can be practiced without departing from the true scope and spirit of the invention.

TABLE OF SEQUENCES

Design8.mosaic1 Amino Acid Sequence                                                   SEQ ID NO: 1  MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGMGWAGWLLSPRG SRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGV RVLEDGVNYATGNLPGCSFSIFLLALLSCLTIPASAYEVRNVSGVYHVTNDCSN SSIVYEAADMIMHTPGCVPCVRENNSSRCWVALTPTLAARNASVPTTTIRRHVD LLVGAAAFCSAMYVGDLCGSVFLVSQLFTFSPRRHETVQDCNCSIYPGHITGHR MAWDMMMNWSPTTALVVSQLLRIPQAVVDMVAGAHWGVLAGLAYYSMVGN WAKVLIVMLLFAGVDGHTHVTGGRVASSTQSLVSWLSQGPSQKIQLVNTNGS WHINRTALNCNDSLQTGFLAALFYVHKFNSSGCPERMASCRPIDEFAQGWGPI THVVPNISDQRPYCWHYAPRPCGIVPASQVCGPVYCFTPSPVVVGTTDRFGVP TYSWGENETDVLLLNNTRPPQGNWFGCTWMNSTGFTKTCGGPPCNIGGVGN NTLTCPTDCFRKHPEATYTKCGSGPWLTPRCLVDYPYRLWHYPCTVNFTIFKV RMYVGGVEHRLNAACNWTRGERCDLEDRDRSELSPLLLSTTEWQILPCSFTTL PALSTGLIHLHQNIVDVQYLYGIGSAVVSFAIKWEYVVLLFLLLADARVCACLWM MLLIAQAEAALENLVVLNAASVAGAFIGILSFLVFFCAAVVYIKGRLVPGAAYALYG VWPLLLLLLALPPRAYAMDREMAASCGGAVFVGLALLTLSPHYKVFLARLIWWL QYFITRAEAHLQVWVPPLNVRGGRDAIILLTCAVHPELIFDITKLLLAILGPLMVLQ AGITRVPYFVRAQGLIRACMLVRKVAGGHYVQMAFMKLAALTGTYVYDHLTPL RDWAHAGLRDLAVAVEPWFSDMETKIITWGADTAACGDIILGLPVSARRGREIL LGPADSLEGQGWRLLAPITAYAQQTRGLLGCIITSLTGRDKNQVEGEVQVVSTA TQSFLATCINGVCWTVYHGAGSKTLAGPKGPITQMYTNVDQDLVGWQAPPGA RSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPLLC PSGHAVGIFRAAVCTRGVAKAVDFIPVESMETTMRSPVFTDNSSPPAVPQTFQ VAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGVDPN IRTGVRTITTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGTVLD QAETAGARLVVLATATPPGSVTVPHPNIEEVALSTTGEIPFYGKAIPIETIKGGRH LIFCHSKKKCDELAAKLSGLGLNAVAYYRGLDVSVIPTSGDVVVVATDALMTGF TGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGKPGI YRFVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETSVRLRAYLNTPGLPVC QDHLEFWESVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARAQAPPPSW DQMWKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMACMSADLEWTST VVVLVGGVLAALAAYCLTTGSVVIVGRIILSGKPAIIPDREVLYREFDEMEECASHL PYIEQGMQLAEQFKQKALGLLQTATKQAEAAAPWESKWRALEAFWAKHMWN FISGIQYLAGLSTLPGNPAIASLMAFTASITSPLTTQHTLLFNILGGWVAAQLAPP SAASAFVGAGIAGAAVGSIGLGKVLVDILAGYGAGVAGALVAFKIMSGEVPSTE DLVNLLPAILSPGALWGWCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVSP THYVPESDAAARVTQILSSLTITQLLKRLHQWINEDCSTPCSGSWLRDVWDWIC TVLTDFKTWLQSKLLPRLPGVPFFSCQRGYKGVWRGDGIMQTTCPCGAQITGH VKNGSMRIVGPKTCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAAEEYV EVTRVGDFHYVTGMTTDNVKCPCQVPAPEFFTEVDGVRLHRYAPACKPLLREE VTFQVGLNQYLVGSQLPCEPEPDVAVLTSMLTDPSHITAETAKRRLARGSPPSL ASSSASQLSAPSLKATCTTHHDSPDADLIEANLLWRQEMGGNITRVESENKVVI LDSFDPLRAEEDEREVSVPAEILRKSRKFPPALPIWARPDYNPPLLESWKDPDY VPPWHGCPLPPTKAPPIPPPRRKRTWLTESTVSSALAELATKTFGSSESSAV DSGTATAPPDQPSDDGDAGSDVESYSSMPPLEGEPGDPDLSDGSWSTVSEE ASEDVVCCSMSYTWTGALITPCAAEESKLPINALSNSLLRHHNMVYATTSRSAS QRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSVEEACKLTPPHSARS KFGYGAKDVRCHARKAVNHINSVWKDLLEDTETPIDTTIMAKNEVFCVQPEKG GRKPARLIVFPDLGVRVCEKMALYDWSTLPQAVMGSSYGFQYSPGQRVEFLV NAWKSKKTPMGFSYDTRCFDSTVTESDIRVEESIYQCCDLAPEARQAIRSLTER LYIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKASAACRAAKLQDCT MLVCGDDLWICESAGTQEDAASLRVFTEAMTRYSAPPGDPPQPEYDLELITSC SSNVSVAHDASGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMYAPTL WARMILMTHFFSILLAQEQLEKALDCQIYGACYSIEPLDLPQIIQRLHGLSAFSLH SYSPGEINRVASCLRKLGVPPLRVWRHRARSVRAKLLSQGGRAATCGKYLFN WAVRTKLKLTPIPAASQLDLSGWFVAGYSGGDIYHSLSRARPRWFMWCLLLLS VGVGIYLLPNR

Design11.mosaic1 Amino Acid Sequence                                                   SEQ ID NO: 2  MSTNPKPQRRTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRAPRKT SERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGMGWAGWLLSPRG SRPSWGPNDPRRRSRNLGRVIDTLTCGFADLMGYIPLVGAPLGGVARALAHGV  RVLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSTGLYHVTNDCPN SSIVYEAADAILHTPGCVPCVREGNASRCWVAVTPTVATRDGKLPTTQLRRHID LLVGSATLCSALYVGDLCGSVFLVGQLFTFSPRRHWTTQDCNCSIYPGHITGHR MAWDMMMNWSPTAALVVAQLLRIPQAILDMIAGAHWGVLAGIAYFSMVGNWA KVLVVLLLFAGVDGHTHVTGGRVASSTQSLVSWLSQGPSQKIQLVNTNGSWHI NRTALNCNDSLQTGFIAALFYAHRFNASGCPERMASCRPLADFDQGWGPISYA NGSGPDQRPYCWHYPPKPCGIVPAKSVCGPVYCFTPSPVVVGTTDRSGAPTY NWGENDTDVFVLNNTRPPLGNWFGCTWMNSSGFTKVCGAPPCVIGGVGNNT LHCPTDCFRKHPEATYSRCGSGPWITPRCLVDYPYRLWHYPCTINYTIFKVRMY VGGVEHRLEAACNWTRGERCDLEDRDRSELSPLLLSTTEWQILPCSFTTLPAL STGLIHLHQNIVDVQYLYGVGSSIASWAIKWEYVVLLFLLLADARVCSCLWMMLL ISQAEAALENLVILNAASLAGTHGLVSFLVFFCFAWYLKGRWVPGAVYALYGM WPLLLLLLALPQRAYALDTEVAASCGGWLVGLMALTLSPYYKRYISWCLWWL QYFLTRVEAQLHVWVPPLNVRGGRDAVILLMCWHPTLVFDITKLLLAVFGPLWI LQASLLKVPYFVRVQGLLRICALARKMAGGHYVQMAIIKLGALTGTYVYNHLTPL RDWAHNGLRDLAVAVEPWFSQMETKLITWGADTAACGDIINGLPVSARRGREI LLGPADGMVSKGWRLLAPITAYAQQTRGLLGCIITSLTGRDKNQVEGEVQIVST AAQTFLATCINGVCWTVYHGAGTRTIASPKGPVIQMYTNVDKDLVGWPAPQGA RSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPLLC PAGHAVGIFRAAVCTRGVAKAVDFIPVENLETTMRSPVFTDNSSPPAVPQSFQV AHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLSFGAYMSKAHGVDPNI RTGVRTITTGSPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGTVLD QAETAGARLVVLATATPPGSITVPHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRH LIFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVATDALMTGYT GDFDSVIDCNTCVIQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKPGIYR FVAPGERPSGMFDSSILCECYDAGCAVVYELTPAETTVRLRAYMNTPGLPVCQD HLEFWEGVFTGLTHIDAHFLSQTKQSGENLPYLVAYQATVCARAQAPPPSWDQ MWKCLTRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMTCMSADLEVATSTW VLVGGVLAALAAYCLSTGCVVIVGRIVLSGKPAIIPDREVLYREFDEMEECSQHL PYIEQGMMLAEQFKQKALGLLQTASRQAEVIAPAVQTNWQKLEAFWAKHMWN FISGVQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTSQTLLFNILGGWVAAQLAA PGAATAFVGAGLAGAAIGSVGLGKVLVDILAGYGAGVAGALVAFKIMSGEVPST EDLVNLLPAILSPGALVVGVVCAAVLRRHVGPGEGAVQWMNRLIAFASRGNHV SPTHYVPESDAAARVTAILSSLTVTQLLRRLHQWISSECTTPCSGSWLRDIWDW ICEVLSDFKTWLKAKLMPQLPGIPFVSCQRGYRGVWRGDGIMHTRCHCGAEIT GHVKNGTMRIVGPRTCRNMWSGTFPINAYTTGPCTPLPAPNYTFALWRVSAEE YVEIRQVGDFHYVTGMTTDNLKCPCQVPSPEFFTELDGVRLHRFAPPCKPLLR EEVSFRVGLHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAGRRLARGSP PSVASSSASQLSAPSLKATCTANHDSPDAELIEANLLWRQEMGSNITRVESENK VVVLDSFDPLVAEEDEREISVPAEILRKSRRFAQALPVWARPDYNPPLLETWKK PDYEPPVVHGCPLPPPQSPPVPPPRKKRTVVLTESTVSTALAELATKSFGSSST SGITGDNTTTSSEPAPSGCPPDSDAESYSSMPPLEGEPGDPDLSDGSWSTVS SGADTEDVVCCSMSYSWTGALVTPCAAEEQKLPINALSNSLLRHHNLVYSTTS RSACQRQKKVTFDRLQVLDSHYQDVLKEVKAAASKVKANLLSVEEACSLTPPH SAKSKFGYGAKDVRCHARKAVNHINSVWKDLLEDSVTPIDTTIMAKNEVFCVQP EKGGRKPARLIVYPDLGVRVCEKMALYDWSKLPLAVMGSSYGFQYSPGQRVE FLVQAWKSKKTPMGFSYDTRCFDSTVTESDIRTEEAIYQCCDLDPQARVAIKSL TERLYVGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKARAACRAAGLQ DCTMLVCGDDLVVICESAGVQEDAASLRAFTEAMTRYSAPPGDPPQPEYDLELI TSCSSNVSVAHDGAGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMFA PTLWARMILMTHFFSVLIARDQLEQALDCEIYGACYSIEPLDLPPIIQRLHGLSAF SLHSYSPGEINRVAACLRKLGVPPLRAWRHRARSVRARLLSRGGRAAICGKYL FNWAVRTKLKLTPIAAAGQLDLSGWFTAGYSGGDIYHSVSHARPRWFWFCLLL LAAGVGIYLLPNR

Design11.mosaic2 Amino Acid Sequence SEQ ID NO: 3 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERSQPRGRRQPIPKARQPEGRAWAQPGYPWPLYGNEGCGWAGWLLSPRG SRPSWGPTDPRRRSRNLGKVIDTLTCGLADLMGYIPLVGAPLGGAARALAHGV RVVEDGVNYATGNLPGCPFSIFLLALLSCLTIPASAYEVRNVSGVYHVTNDCSN SSIVYEAADMIMHTPGCVPCVRENNSSRCWVALTPTLAARNASVPTTTIRRHVD LLVGAAAFCSAMYVGDLCGSVFLVSQLFTFSPRRHETVQDCNCSIYPGHVSGH RMAWDMMMNWSPTTALWSQLLRIPQAVVDMVAGAHWGVLAGLAYYSMVGN WAKVLIVMLLFAGVDGGTYVTGGTMAKNTLGITSLFSPGSSQKIQLINTNGSWHI NSTALNCNDSLNTGFLAALFYTHRFNSSGCPERMASCRPIDKFAQGWGPITHV VPNISDQRPYCWHYAPRPCGIVPASQVCGPVYCFTPSPWVGTTDRFGVPTYS WGENETDVLLLNNTRPPQGNWFGCTWMNSTGFTKTCGGPPCNIGGVGNNTL TCPTDCFRKHPEATYTKCGSGPWLTPRCMVDYPYRLWHYPCTVNFTIFKVRM YVGGVEHRLNAACNWTRGERCNLEDRDRSELSPLLLSTTQWQVLPCSFTTLP ALTTGLIHLHQNWDVQYLYGIGSAWSFAIKWEYVLLLFLLLADARVCACLWMM LLIAQAEAALENLVVLNAASVAGAHGILSFLVFFCAAWYIKGRLVPGAAYALYGV WPLLLLLLALPPRAYAMDREMAASCGGAVFVGLVLLTLSPHYKVFLARLIWWLQ YFITRAEAHLQVWIPPLNVRGGRDAIILLTCAVHPELIFDITKLLLAILGPLMVLQA GITRVPYFVRAQGLIRACMLVRKVAGGHYVQMAFMKLAALTGTYVYDHLTPLR DWAHAGLRDLAVAVEPWFSDMETKIITWGADTAACGDIILGLPVSARRGKEILL GPADSLEGQGWRLLAPITAYSQQTRGLLGCIVTSLTGRDRNQVEGEVQWSTA TQSFLATCVNGVCWTVYHGAGSKTLAGPKGPITQMYTNVDQDLVGWQAPPGA RSLTPCACGSSDLYLVTRHADVIPVRRRGDGRGSLLSPRPVSYLKGSSGGPLL CPSGHAVGIFRAAVCTRGVAKAVDFVPVESMETTMRSPVFTDNSSPPAVPQTF QVAHLHAPTGSGKSTRVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDP NIRTGVRTITTGAPITYSTYGKFLADGGCSGGAYDIIMCDECHSTDSTTILGIGTV LDQAETAGARLTVLATATPPGSVTVPHPNIEEVALSNTGEIPFYGKAIPIETIKGG RHLIFCHSRKKCDELAAKLSGLGLNAVAYYRGLDVSVIPASGDVVVVATDALMT GFTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGR RGIYRFVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETSVRLRAYLNTPGL PVCQDHLEFWESVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARAQALP PSWDQMWKCLIRLKPTLHGPTPLLYRLGAVQNEITLTHPITKYIMACMSADLEW TSTWVLVGGVLAALAAYCLTTGSWIVGRIILSGKPAVIPDREVLYQEFDEMEEC ASHLPYIEQGMQLAEQFKQKALGLLQTATKQAEAAAPVVESKWRALETFWAKH MWNFISGIQYLAGLSTLPGNPAIASLMAFTASITSPLTTQHTLLFNILGGWVAAQL APPSAASAFVGAGIAGAAVGSIGLGKVLVDILAGYGAGVAGALVAFKVMSGEMP STEDLVNLLPAILSPGALWGWCAAILRRHVGPGEGAVQWMNRLIAFASRGNH VSPTHYVQESDAAARVTQILSSLTITQLLKRLHQWINEDCSTPCSGSWLRDVWD WICTVLTDFKTWLQSKLLPRLPGVPFFSCQRGYKGVWRGDGIMQTTCPCGAQI TGHVKNGSMRIVGPKTCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAAE EYVEVTRVGDFHYVTGMTTDNVKCPCQVPAPEFFTEVDGVRLHRYAPACKPLL REEVTFQVGLNQYLVGSQLPCEPEPDVTVLTSMLTDPSHITAETAKRRLARGSP PSLASSSASQLSAPSLKATCTTRHDSPDADLIEANLLWRQEMGGNITRVESENK WILDSFDPLRAEEDEREVSVPAEILRKSRKFPPALPIWARPDYNPPLLESWKDP DYVPPVVHGCPLPPTKAPPIPPPRRKRTVVLTESTVSSALAELATKTFGSSESS AVDSGTATAPPDQPSDDGDAGSDVESYSSMPPLEGEPGDPDLSDGSWSTVS EEASEDVVCCSMSYTWTGALITPCAAEESKLPINALSNSLLRHHNMVYATTSRS ASQRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSVEEACKLTPPHSA RSKFGYGAKDVRNLSSKAVNHIRSVWKDLLEDTETPIDTTIMAKNEVFVVQPEK GGRKPARLIVFPDLGVRVCEKMALYDVVSTLPQAVMGSSYGFQYSPKQRVEFL VNAWKSKKCPMGFAYDTRCFDSTVTENDIRVEESIYQCCDLAPEARQAIRSLTE RLYIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKASAACRAAKLQDC TMLVNGDDLVVICESAGTQEDAASLRVFTEAMTRYSAPPGDPPKPEYDLELITS CSSNVSVAHDASGKRVYYLTRDPTTPIARAAWETARSTPVNSWLGNIIMYAPTL WARMILMTHFFSILLAQEQLEKALDCQIYGACYSIEPLDLPQIIERLHGLSAFSLH SYSPGEINRVASCLRKLGVPPLRVWRHRARSVRAKLLSQGGRAATCGKYLFN WAVKTKLKLTPIPAASQLDLSGWFVAGYSGGDIYHSLSRARPRWFMWCLLLLS VGVGIYLLPNR

Design14.mosaic1 Amino Acid Sequence SEQ ID NO: 4 MSTNPKPQRQTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRAPRKT SERSQPRGRRQPIPKARRPEGRAWAQPGYPWPLYGNEGMGWAGWLLSPRG SRPSWGPNDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARVLAHGV RVLEDSVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSTGLYHVTNDCPN SSIVYEAADAILHTPGCVPCVREGNASRCWVAMTPTVATRDGKLPTTQLRRHID LLVGSATLCSALYVGDLCGSVFLVGQLFTFSPRRHWTTQDCNCSIYPGHITGHR MAWDMMMNWSPTTALVVSQLLRIPQAVMDMVAGAHWGILAGLAYYSMVGNW AKVLVVLLLFAGVDAGTHVTGGSAAKDTSGFTSLFRIGARQNIQLINTNGSWHIN RTALNCNASLDTGWVAGLFYYHKFNSSGCPERMASCRPLADFDQGWGPISYA NGSGPDQRPYCWHYPPKPCGIVPAKSVCGPVYCFTPSPVVVGTTDRSGAPTY NWGENDTDVFVLNNTRPPLGNWFGCTWMNSSGFTKVCGAPPCVIGGVGNNT LHCPTDCFRKHPEATYSRCGSGPWITPRCLVDYPYRLWHYPCTINYTIFKVRMY VGGVEHRLEAACNWTRGERCDLEDRDRSELSPLLLSTTQWQVLPCSFTPMPA LSTGLIHLHQNIVDVQYLYGVGSSIASWAIKWEYVVLLFLLLADARVCSCLWMML LISQVEAALENLVILNAASLAGTHGLVSFLVFFCFAWYLKGRWVPGAVYALYGM WPLLLLLLALPQRAYALDTEVAASCGGWLVGLMALTLSPYYKRYISWCLWWL QYFLTRVEAQLHVWVPPLNVRGGRDAVILLMCVVHPTLVFDITKLLLAVFGPLWI LQASLLKVPYFVRVQGLLRICALARKMAGGHYVQMAIIKLGALTGTYVYNHLTPL RDWAHNGLRDLAVAVEPWFSQMETKLITWGADTAACGDIINGLPVSARRGREI LLGPADGMVSKGWRLLAPITAYAQQTRGLLGCIVTSLTGRDKNQVEGEVQIVST AAQTFLATCINGVCWTVYHGAGTRTIASPKGPVIQMYTNVDKDLVGWPAPQGA RSLTPCACGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPVSYLKGSSGGPLL CPAGHAVGIFRAAVCTRGVAKAVDFIPVENLETTMRSPVFTDNSSPPVVPQSFQ VAHLHAPTGSGKSTKVPAAYASQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNI RTGVRTITTGASITYSTYGKFLADGGCSGGAYDIIICDECHSTDSTSILGIGTVLD QAETAGVRLTVLATATPPGSVTVPHSNIEEVALSTTGEIPFYGKAIPLEVIKGGRH LIFCHSKKKCDELAAKLVALGVNAVAYYRGLDVSVIPASGDVWVATDALMTGY TGDFDSVIDCNTCVTQSVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKPGI YRFVAPGERPSGMFDSVVLCECYDAGCAVVYELTPSETTVRLRAYMNTPGLPV CQDHLEFWESVFTGLTHIDAHFLSQTKQSGENFPYLVAYQATVCARAQALPPS WDQMWKCLVRLKPTLHGPTPLLYRLGAVQNEVTLTHPVTKYIMTCMSADLEVV TSTWVLVGGVLAALAAYCLSTGCVVIVGRIVLSGKPAIIPDREVLYREFDEMEEC SQHLPYIEQGMALAEQFKQKALGLLQTASRQAEVIAPAVQTNWQKLEAFWAKH MWNFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTSQTLLFNILGGWLAAQ LAAPGAATAFVGAGLAGAAIGSVGLGKVLVDILAGYGAGVAGALVAFKVMSGD MPSTEDLVNLLPAILSPGALWGVVCAAILRRHVGPGEGAVQWMNRLIAFASRG NHVSPTHYVPESDAAARVTTILSSLTVTQLLRRLHQWISSESTTPCSGSWLKDV WDWICTVLSDFKTWLQSKLLPRLPGVPFFSCQRGYKGVWRGDGIMHTTCPCG AQITGHVKNGSMRIVGPRTCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRV AAEEYVEVTRVGDFHYVTGMTTDNIKCPCQVPAPEFFTELDGVRLHRYAPACK PLLREEVTFQVGLNQYLVGSQLPCEPEPDVTVVTSMLTDPSHITAEAARRRLAR GSPPSVASSSASQLSAPSLKATCTTHHDSPDADLIEANLLWRQEMGSNITRVES ENKWILDSFEPLRAEEDEREVSVAAEILRKSRKFPPALPVWARPDYNPPLIESW KDPDYVPPVVHGCPLPPTKAPPIPPPRRKKTVVLTESTVSSALAELATKTFGSS GSSAVDSGTATAPPDQPSDDGDAGSDVESYSSMPPLEGEPGDPDLSDGSWS TVSEEASEDVVCCSMSYSWTGALITPCAAEESKLPINALSNSLLRHHNMVYATT SRSASQRQKKVTFDRLQVLDNHYQDVLKEMKAKASTVKAKLLSVEEACKLTPP HSARSKFGYGAKDVRNLSSKAVNHIRSVWKDLLEDTETPIDTTIMAKSEVFCVQ PEKGGRKPARFIVFPDLGVRVCEKMALYDVVSTLPQAVMGSSYGFQYSPKQR VEFLVNTWKSKKCPMGFSYDTRCFDSTVTESDIRVEESIYQCCDLAPEARQAIR SLTERLYIGGPLTNSKGQSCGYRRCRASGVLTTSCGNTLTCYLKASAACRAAKL QDCTMLVNGDDLVVICESAGTQEDAASLRVFTEAMTRYSAPPGDLPQPEYDLE LITSCSSNVSVAHDATGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMF APTLWVRMILMTHFFSILLAQEQLEKALDCQIYGATYSIEPLDLPQIIQRLHGLSA FSLHSYSPGEINRVASCLRKLGVPPLRVWRHRARSVRAKLLSQGGRAAICGRY LFNWAVRTKLKLTPIPAASQLDLSGWFVAGYSGGDIYHSLSRARPRWFMWCLL LLSVGVGIYLLPNR

Design14.mosaic2 Amino Acid Sequence SEQ ID NO: 5 MSTNPKPQRKIKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRTTRKTS ERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRGS RPSWGPSDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVR VLEDGVNYATGNLPGCSFSIFLLALLSCLTIPASAYEVRNASGVYHVTNDCSNSS IVYEAADVIMHTPGCVPCVREGNSSRCWVALTPTLAARNSSIPTTTIRRHVDLLV GAAALCSAMYVGDLCGSVFLVSQLFTFSPRRYETVQDCNCSIYPGHVSGHRM AWDMMMNWSPTTALWAQLLRIPQAILDMIAGAHWGVLAGIAYFSMVGNWAK VIVVLLLFAGVDGNTRVSGGEAAKNTMGFASLFVSGPSQKIQLINTNGSWHINR TALNCNDSLQTGFLAALFYAHKFNASGCPERMASCRPIDEFAQGWGPITHVVP NISDQRPYCWHYAPRPCGIVPASQVCGPVYCFTPSPVVVGTTDRSGVPTYTW GENETDVLILNNTRPPRGNWFGCTWMNSTGFTKTCGGPPCNIGGAGNNTLICP TDCFRKHPEATYARCGSGPWLTPRCMVDYPYRLWHYPCTVNYTLFKVRMYVG GVEHRLNAACNWTRGERCDLDDRDRSELSPLLLSTTEWQILPCSFTTLPALTT GLIHLHQNIVDVQYLYGVGSSIVSWAIKWEYVILLFLLLADARICSCLWMMLLISQ AEAALENLVLLNAASLAGVHGILSFLVFFCAAVVYIKGRLVPGAAYAFYGVWPLLL LLMALPARAYAMDREMAASCGGAVFVGLVLLTLSPYYKVFLAKLIWWLQYLITR AEAHLQVWVPPLNVRGGRDAIILLTCAVHPELIFDITKLLLAILGPLMVLQAGITRV PYFVRAQGLIRACMLVRKAAGGHYVQMAFMKLAALTGTYVYDHLTPLQDWAH TGLRDLAVAVEPVIFSDMETKIITWGADTAACGDIISGLPVSARRGKEILLGPADS FGEQGWRLLAPITAYSQQTRGLLGCIITSLTGRDKNQVEGEVQMVSTATQSFLA TCINGACWTVYHGAGSKTLAGPKGPITQMYTNVDQDLVGWPAPPGARSMTPC TCGSSDLYLVTRHADVIPVRRRGDTRGSLLSPRPISYLKGSSGGPLLCPSGHVV GIFRAAVCTRGVAKAVDFIPVESLETTMRSPVFTDNSSPPAVPQSFQVAYLHAP TGSGKSTKVPAAYAAQGYTVLVLNPSVAATLSFGAYMSKAHGVDPNIRTGVRTI TTGSPITYSTYGKFLADGGCSGGAYDIIMCDECHSTDATSILGIGTALDQAETAG ARLVVLATATPPGSITVPHPNIEEVALSNTGEIPFYGKAIPLEAIKGGRHLIFCHSK RKCDELAAKLVALGINAVAYYRGLDVSVIPTSGNVVVVATDALMTGFTGDFDSVI DCNTCVTQTVDFSLDPTFTIETTTVPQDAVSRTQRRGRTGRGRRGIYRFVTPG ERPSGMFDSSVLCECYDAGCAVVYELTPAETSVRLRAYLNTPGLPVCQDHLEF WEGVFTGLTRIDAHFLSQTKQAGDNFPYLVAYQATVCARSQAPPPSWDQMWK CLIRLKPTLHGATPLLYRLGAVQNEITLTHPITKYIMACMSADLEVVTSTWVLVG GVLAALAAYCLTTGCVVIVGRVVLSGKPAIVPDREVLYRQFDEMEECSQHLPYI EQGMMLAEQFKQKALGLLQTATKQAEAAAPMVESKWRALETFWAKHMWNFIS GVQYLAGLSTLPGNPAIASLMAFTASVTSPLTTQSTLLFNILGGWVAAQLAPPSA ASAFVGAGIAGAAVGSIGLGKVLVDVLAGYGAGVAGALVAFKVMSGEMPSTED LVNLLPAILSPGALVVGVVCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVSPT HYVPESDAAARVTQILSSLTITQLLKRLHQWINEDCSTPCSGSWLRDVWDWICT VLTDFKTWLQSKLMPRLPGVPFLSCQRGYKGVWRGDGIMQTTCPCGAQIAGH VKNGSMRIVGPKTCSNTWHGTFPINAYTTGPCTPLPAPNYKFALWRVSAEEYV EVRQVGDFHYVTGMTTDNVKCPCQVPAPEFFTEVDGVRLHRYAPPCKPLLRD EVTFQVGLNQYVVGSQLPCEPEPDVTVLTSMLTDPSHITAETAKRRLARGSPPS LASSSASQLSAPSLKATCTTRHDSPDADLIEANLLWRQAMGGNITRVESENKVV VLDSFDPLRAEEDEREVSVPAEILRRSRKFPPAMPIWARPDYNPPLLESWKDP DYVPPVVHGCPLPPAKAPPIPPPRRKRTVVLTESSVSSALAELATKTFGSSESS AVDSGTATGPPDQASDDGDKGSDVESYSSMPPLEGEPGDPDFSDGSWSTVS SGADTEDVVCCSMSYTWTGALITPCAAEESKLPINPLSNSLLRHHSMVYSTTSR SASLRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSIEEACKLTPPHSA KSKFGYGAKDVRSLSSRAVNHIRSVWEDLLEDTETPIDTTVMAKNEVFCIQPEK GGRKPARLIVYPDLGVRVCEKMALYDVVSTLPQAVMGPSYGFQYSPGQRVEFL VNAWKSKKNPMGFAYDTRCFDSTVTENDIRVEESIYQCCDLAPEARQAIKSLTE RLYIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYIKAQAACRAAGLRDC TMLVCGDDLVVICESQGVQEDAANLRAFTEAMTRYSAPPGDPPQPEYDLELITS CSSNVSVAHDGAGKRVYYLTRDPTTPLARAAWETARHTPINSWLGNIIMFAPTL WARMILMTHFFSVLIARDQLEQALDCEIYGACYSIEPLDLPPIIQRLHGLSAFSLH SYSPGEINRVATCLRKLGVPPLRAWRHRARNVRARLLSRGGRAAICGKYLFNW AVKTKLKLTPIAAAGQLDLSGWFTAGYSGGDIYHSVSRARPRWFWFCLLLLAA GVGIYLLPNR

Design14.mosaic3 Amino Acid Sequence SEQ ID NO: 6 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERSQPRGRRQPIPKARQPEGRAWAQPGYPWPLYGNEGLGWAGWLLSPRG SRPSWGPTDPRRRSRNLGKVIDTLTCGLADLMGYIPLVGAPLGGVARALAHGV RVVEDGVNYATGNLPGCSFSIFLLALLSCLTTPASAYEVRNVSGVYHVTNDCSN ASIVYEAADMIMHTPGCVPCVRENNSSRCWVALTPTLAARNASVPTTTIRRHVD LLVGAAAFCSAMYVGDLCGSVFLISQLFTFSPRRHETVQDCNCSIYPGHVTGHR MAWDMMMNWSPTAALVVSQLLRIPQAVVDMVAGAHWGVLAGLAYYSMAGN WAKVLIVMLLFAGVDGGTYVTGGTMAKNTLGITSLFSPGSSQKIQLVNTNGSW HINSTALNCNDSLNTGFLAALFYTHRFNSSGCPERLASCRPLTDFAQGWGPITY AGSRSPDQRPYCWHYAPQPCGIVPAAQVCGPVYCFTPSPVWGTTDRFGVPT YSWGENETDVLLLNNTRPPQGNWFGCTWMNGTGFTKTCGAPPCNIGGVGNN TLTCPTDCFRKHPEATYTKCGSGPWLTPRCLVHYPYRLWHYPCTVNFTIFKVR MYVGGVEHRLDAACNWTRGERCNLEDRDRSELSPLLLSTTEWQVLPCSFTTL PALSTGLIHLHRNIVDVQYLYGIGSAVVSFAIKWEYVLLLFLLLADARVCACLWM MLLIAQAEAALENLVVLNAASVAGAFIGILSFLVFFCAAVVYIKGKLVPGAAYALYG VWPLLLLLLALPPRAYAMDREVAASCGGAVFIGLALLTLSPHYKVFLARLIWWLQ YFITRAEAHLQVWIPPLNVRGGRDAIILLTCAIHPELIFTITKILLAILGPLMVLQAGL TRVPYFVRAHGLIRACMLVRKVAGGHYVQMALMKLAALTGTYVYDHLTPLRDW AHAGLRDLAVAVEPVVFSDMETKVITWGADTAACGDIILGLPVSARRGKEIFLGP ADSLEGQGWRLLAPITAYSQQTRGLFGCIITSLTGRDRNQVEGEVQVVSTATQS FLATCVNGVCWTVFHGAGSKTLAGPKGPIIQMYTNVDQDLVGWQAPPGARSL TPCTCGSSDLYLVTRHADVIPVRRRGDGRGSLLSPRPVSYLKGSSGGPLLCPS GHAVGIFRAAVCTRGVAKAVDFVPVESMETTMRSPVFTDNSSPPAVPQTFQVA HLHAPTGSGKSTRVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAYGTDPNIR TGVRTITTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSTDSTTILGIGTVLDQ AETAGARLTVLATATPPGSVTVPHPNIEEVALSNIGEIPFYGKAIPIETIKGGRHLI FCHSRKKCDELAAKLSGLGLNAVAYYRGLDVSVIPTSGDWWATDALMTGYT GDFDSVIDCNTCVIQTVDFSLDPTFTIDTTTVPQDAVSRSQRRGRTGRGRGGIY RFVTPGERPSGMFDSSILCECYDAGCAWYELTPAETTVRLRAYLNTPGLPVCQ DHLEFWEGVFTGLTHIDAHFLSQTKQSGENLPYLVAYQATVCARAQAPPPSWD QMWKCLTRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKFIMACMSADLEWTST WVLVGGVLAALAAYCLTTGSVVIVGRIILSGKPAVIPDREVLYQEFDEMEECASH LPYIEQGMQLAEQFKQKALGLLQTASKQAEAAAPWESKWRALEAFWAKHMW NFISGIQYLAGLSTLPGNPAIVSLMAFTASITSPLTTQHTLLFNILGGWVAAQLAA PGAATAFVGAGLAGAAVGSVGLGKVLVDIIAGYGAGVAGALVAFKIMSGEVPST EDLVNLLPAILSPGALVVGVVCAAVLRRHVGPGEGAVQWMNRLIAFASRGNHV SPTHYVQESDAAARVTAILSSLTVTQLLRRLHQWISSECTTPCSGSWLRDIWD WICEVLSDFKTWLKAKLMPQLPGIPFVSCQRGYRGVWRGDGIMHTRCHCGAEI TGHVKNGTMRIVGPRTCRNMWSGTFPINAYTTGPSTPLPAPNYTFALWRVSAE EYVEIRQVGDFHYVTGMTTDNLKCPCQVPSPEFFTELDGVRLHRFAPPCKPLL REEVSFRVGLHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAGRRLARGS PPSMASSSASQLSAPSLKATCTANHDSPDAELIEANLLWRQEMGGNITRVESE NKVVILDSFDPLVAEEDEREISVPAEILRKSRRFAPALPIWARPDYNPPLLETWK KPDYEPPVVHGCPLPPPQSPPVPPPRKKRTVVLTESTVSTALAELATKSFGSSS TSGITGDNTTTSSEPAPSGCPPDSDAESYSSMPPLEGEPGDPDLNDGSWSTV SSEAGTEDWCCSMSYSWTGALVTPCAAEEQKLPINALSNSLLRHHNLVYSTT SRSACQRQKKVTFDRLQVLDSHYQDVLKEVKAAASKVKANLLSVEEACSLTPP HSARSKYGYGAKDVRCHARKAVNHINSVWKDLLEDSVTPIDTTIMAKNEVFCV QPERGGRKPARLIVFPDLGVRVCEKMALYDVVSKLPLAVMGSSYGFQYSPGQ RVEFLVQAWKSKKTPMGFSYDTRCFDSTVTESDIRTEEAIYQCCDLDPQARVAI KSLTERLYVGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKARAACRAA GLQDCTMLVCGDDLVVICESAGVQEDAASLRAFTEAMTRYSAPPGDPPKPEYD LELITSCSSNVSVAHDASGKRVYYLTRDPTTPLGRAAWETVRHTPVNSWLGNII MYAPTLWARMVLMTHFFSILIAQEQLEKALDCQIYGACYSIEPLDLPQIIERLHGL SAFTLHSYSPGEINRVAACLRKLGVPPLRAWRHRARSVRARLLSQGGRAATCG KYLFNWAVRTKLKLTPIPAASRLDLSGWFTAGYSGGDIYHSVSHARPRWFMLC LLLLSVGVGVYLLPNR

Design16.mosaic1 Amino Acid Sequence SEQ ID NO: 7 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRAPRKT SERSQPRGRRQPIPKARRPEGRTWAQPGFPWPLYGNEGCGWAGWLLSPRG SRPSWGPSDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARVLAHGV RVLEDGVNYATGNLPGCPFSIFLLALLSCLTIPASAYEVRNASGVYHVTNDCPN SSIVYETADMIMHTPGCVPCVREGNSSRCWVALTPTLAARNSSIPTTTIRRHVD LLVGTAAFCSAMYVGDLCGSVFLVSQLFTFSPRHHWTTQGCNCSIYPGHVSGH RMAWDMMMNWSPTAALVVAQLLRIPQAILDMIAGAHWGVLAGMAYFSMVGN WAKVLIVMLLFAGVDGHTHVTGGRVASSTQSLVSWLSQGPSQKIQLVNTNGS WHINRTALNCNDSLQTGFIAALFYAHRFNASGCPERMASCRPIDKFAQGWGPIT HVVPNISDQRPYCWHYAPQPCGIVPASEVCGPVYCFTPSPVVVGTTDRFGVPT YSWGENETDVLLLNNTRPPQGNWFGCTWMNSTGFTKTCGGPPCNIGGVGNN TLICPTDCFRKHPEATYTKCGSGPWLTPRCLVDYPYRLWHYPCTVNFTVFKVR MYVGGVEHRLNAACNWTRGERCDLEDRDRSELSPLLLSTTEWQILPCSFTTLP ALSTGLIHLHQNIVDIQYLYGIGSAAVSFAIKWEYVLLLFLLLADARVCACLWMML LIAQAEAALENLVVLNAASLAGAHGVFSFLVFFCAAWYIKGRLVPGAAYALYGV WPLLLLLLALPPRAYAMDREMAASCGGAVFIGLALLTLSPHYKVFLARLIWWLQ YFITRAEAHLQVWVPPLNVRGGRDAIILLACAVHPELIFDITKLLLAILGPLMVLQA GITRVPYFVRAQGLIRACMLVRKVAGGHYVQMAFMKLAALTGTYVYDHLTPLR DWAHAGLRDLAVAVEPVIFSDMETKIITWGADTAACGDIISGLPVSARRGKEILL GPADSFGEQGWRLLAPITAYAQQTRGLLGCIVTSLTGRDKNQVDGEVQVLSTA TQSFLATCVNGVCWTVFHGAGSKTLAGPKGPITQMYTNVDQDLVGWPAPPGA RSMTPCTCGSSDLYLVTRHADWPVRRRGDSRGSLLSPRPVSYLKGSSGGPLL CPSGHVVGIFRAAVCTRGVAKAVDFIPVESMETTMRSPIFTDNSSPPAVPQTFQ VAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLSFGAYMSKAHGTDPN IRTGVRTITTGAPITYSTYGKFLADGGCSGGAYDIIMCDECHSTDSTTILGIGTVL DQAETAGARLVVLATATPPGSITVPHPNIEEVALSNTGEIPFYGKAIPLEAIKGGR HLIFCHSRKKCDELAAKLVALGVNAVAYYRGLDVSVIPTSGDVVVVATDALMTG YTGDFDSVIDCNTCVTQTVDFSLDPTFTIDTTTVPQDAVSRSQRRGRTGRGRM GIYRFVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETTVRLRAYLNTPGLP VCQDHLEFWEGVFTGLTRIDAHFLSQTKQSGENFPYLVAYQATVCARAQALPP SWDQMWKCLTRLKPTLHGPTPLLYRLGAVQNEITLTHPITKYIMTCMAADLEW TSTWVLVGGVLAALAAYCLTTGSVVIVGRIILSGRPAVVPDREVLYQQFDEMEE CASHLPYIEQGMQLAEQFKQKALGLLQTATKQAEAAAPMVESKWRALETFWAK HMWNFISGIQYLAGLSTLPGNPAIASLMAFTASITSPLTTQSTLLFNILGGWVAA QLAAPGAATAFVGAGLAGAAVGSVGLGKVLIDILAGYGAGVAGALVAFKIMSGE VPSTEDLVNLLPAILSPGALVVGWCAAILRRHVGPGEGAVQWMNRLIAFASRG NHVSPTHYVQESDAAARVTAILSSLTVTQLLRRLHQWISSDCTTPCSDSWLRDI WDWICEVLSDFKTWLKAKLMPQLPGIPFVSCQRGYRGAWRGDGIMHTRCHCG AEITGHVKNGTMRIVGPRTCRNMWSGTFPINAYTTGPCTPLPAPNYTFALWRV SAEEYVEIRRVGDFHYVTGMTTDNLKCPCQVPSPEFFTELDGVRLHRYAPPCK PLLREEVSFRVGLHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAKRRLAR GSPPSEASSSASQLSAPSLKATCTANHDSPDAELIEANLLWRQEMGGDITRVE SKNKWILDSFDPLVAEEDEREISVPAEILRKSRRFAQALPVWARPDYNPPLVET WKKPDYEPPWHGCPLPPAKAPPIPPPRRKRTWLTESTVSTALAELATKSFGS SSTSGITGDNTTTSSEPASSGCPPDSDAESYSSMPPLEGEPGDPDLNDGSWS TVSSEAGTEDVVCCSMSYSWTGALITPCAAEETKLPINALSNSLLRHHNLVYST TSRSACLRQKKVTFDRLQVLDNHYQDVLKEVKAAASKVKANLLSVEEACSLTPP HSARSKFGYGAKDVRCHARKAVNHINSVWKDLLEDSVTPIDTTIMAKNEVFCVQ PEKGGRKPARLIVYPDLGVRVCEKMALYDVVSKLPLAVMGSSYGFQYSPGQRV EFLVKAWKSKKNPMGFAYDTRCFDSTVTENDIRTEESIYQCCDLAPEARQVIRS LTERLYIGGPLTNSKGQNCGYRRCRASGVLTTNCGNTLTCYIKAQAACRAAGL RDCTMLVCGDDLVVICESQGVQEDAANLRAFTEAMTRYSAPPGDLPQPEYDLE LITSCSSNVSVAHDGAGKRVYYLTRDPATPFARAAWETAKHTPVNSWLGNIIMF APTLWVRMILLTHFFSVLIARDQLEQALNCEIYGACYSIEPLDLPPIIQRLHGLSAF SLHSYSPGEINRVASCLRKLGVPPLRVWRHRARSVRARLLSQGGRAATCGKYL FNWAVKTKLKLTPIPAASRLDLSGWFVAGYSGGDIYHSVSRARPRWFMLCLLLL SVGVGVYLLPNR

Design16.mosaic2 Amino Acid Sequence SEQ ID NO: 8 MSTNPKPQRQTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERPQPRGRRQPIPKARQPEGRAWAQPGHPWPLYGNEGMGWAGWLLSPRG SRPSWGPNDPRRRSRNLGKVIDTLTCGLADLMGYIPLVGAPLGGVARALAHGV RVVEDGVNYATGNLPGCSFSIFLLALLSCLTIPASAYQVRNSTGLYHVTNDCSN SSIVYEAADVIMHTPGCVPCVREDNSSRCWVALTPTLAARNASIPTTAIRRHVDL LVGAAAFCSAMYVGDLCGSVFLISQLFTFSPRRYETVQDCNCSLYPGHVSGHR MAWDMIMNWSPTTALVVSQLLRIPQAVVDMVAGAHWGVLAGLAYYSMVGNW AKVLWMLLFAGVDGGTHVTGGKVAYTTQGFTSFFSRGPSQKIQLVNTNGSWH INRTALNCNDSLNTGFLAALFYAHKFNSSGCSGRMASCRPIDEFAQGWGPITYA EPHDLDQRPYCWHYAPRPCGIVPASTVCGPVYCFTPSPVVVGTTDKSGAPTY NWGENDTDVFVLNNTRPPRGNWFGCTWMNSTGFTKVCGAPPCVIGGVGNNT LRCPTDCFRKHPEATYARCGSGPWLTPRCLVHYPYRLWHYPCTINYTIFKVRM YVGGVEHRLEAACNWTRGERCDLTDRDRSELSPLLLSTTEWQVLPCSFTTLPA LSTGLIHLHRNIVDVQYLYGIGSAVVSFAIKWEYILLLFLLLADARFCACLWMMLL VAQAEAALENLVVLNAASVAGAHGILSFLVFFCAAVVYIKGKLVPGAAYAFYGVW PLLLLLMALPARAYAMDREMAASCGGAVFVGLVLLTLSPYYKVFLAKLIWWLQY LITRAEAHLQVWIPPLNVRGGRDAVILLTCAIHPELIFTITKILLAILGPLMVLQAGIT KVPYFVRAHGLIRACMLVRKVAGGHYVQMALMKLAALTGTYVYDHLTPLQDWA HAGLRDLAVAVEPVVFSRMETKLITWGADTAACGDILSGLPVSARRGKEIFLGP ADSLEGQGWRLLAPITAYSQQTRGLLGCIITSLTGRDKNQVEGEVQIVSTATQT FLATCVNGVCWTVYHGAGTRTIASSKGPVIQMYTNVDQDLVGWPAPQGSRSL TPCTCGSSDLYLVTRHADVIPVRRRGDNRGSLLSPRPISYLKGSSGGPLLCPSG HAAGIFRAAVCTRGVAKAVDFVPVESMETTMRSPVFTDNSTPPAVPQSFQVTH LHAPTGSGKSTRVPAAYAAQGYKVLVLNPSVAATLGFGVYMSKAHGVDPNVRT GVRTITTGSPITYSTYGKFLADGGCSGGAYDIIMCDECHSTDSTSILGIGTVLDQ AETAGVRLTVLATATPPGSVTVPHPNIEEVALSNIGEIPFYGKAIPIEAIKGGRHLI FCHSKKKCDELAAKLSALGLNAVAYYRGLDVSVIPSSGDVVVVATDALMTGFTG DFDSVIDCNTCVIQTVDFSLDPTFTIETTTVPQDAVSRTQRRGRTGRGRGGIYR FVTPGERPSGMFDSSVLCECYDAGCAWYELTPAVTSVRLRAYLNTPGLPVCQ VHLEFWESVFTGLTHIDAHFLSQTKQAGENFPYLTAYQATVCARAQAPPPSWD QMWKCLNRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKFIMACMSADLEWTST WVLVGGVLAALAAYCLSTGCVVIVGRIILSGKPAVIPDREVLYREFDEMEECASQ LPYIEQGMQLAEQFKQKAIGLLQTATKQAEAAAPWESKWRALEAFWAKHMW NFISGIQYLAGLSTLPGNPAIVSLMAFTASITSPLTTQHTLLFNILGGWVAAQLAP PRAASAFVGAGIAGAAVGSIGLGKVLVDILAGYGAGVAGALVAFKVMSGDMPST EDLVNLLPAILSPGALVVGWCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVS PTHYVPESDAAARVTQILSNLTITQLLKRLHQWINEDCSTPCSGSWLRDVWDWI CTVLADFKTWLQSKVLPRLPGVPFFSCQRGYKGVWRGDGIMYTTCPCGAQIT GHVKNGTMRIVGPKTCRNMWSGTFPINAYTTGPCTPLPAPNYKFALWRVSAEE YVEIRQVGDFHYVTGMTADNLKCPCQVPAPEFFTELDGVRLHRFAPPCKPLLR DEVSFRVGLHDYPVGSQLPCEPEPDVAVVTSMLTDPSHITAEAAGRRLARGSP PSVASSSASQLSAPSLKATCTTNHDSPDAELIEANLLWRQEMGGNITRVESENK WVLDSFDPLVAEEDEREVSIPAEILRKSRKFPRAMPIWARPDYNPPLIESWKDP DYVPPVVHGCPLPPPRSPPVPPPRKKRTWLTESTLSTALAELATKSFGSSSTS GITGDDTTTSSEPAPSGCPPDSDAESCSSMPPLEGEPGDPDFSDGSWSTVSS GADTEDVVCCSMSYSWTGALVTPCAAEEQKLPINALSNSLLRHHNMVYSTTSR SACQRQKKVTFDRLQVLDSHYQDVLKEVKAAASTVKANLLSVEEACSLTPPHS AKSKFGYGAKDVRNLSSKAVNHIHSVWKDLLEDSETPIDTTIMAKNEIFCVQPEK GGRKSARLIVFPDLGVRVCEKMALYDVVSKLPVAVMGSSYGFQYSPGQRVEFL VQAWKSKKTPMGFSYDTRCFDSTVTESDIRTEEAIYQCCDLDPQARVAIKSLTE RLYVGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKARAACRAAGLQDC TMLVCGDDLVVICESAGVQEDAASLRAFTEAMTRYSAPPGDPPQPEYDLELITS CSSNVSVAHDGTGKRVYYLTRDPTIPLARAAWETARHTPINSWLGNIIMFAPTL WARMILMTHFFSVLIARDQLEQALDCEIYGACYSIEPLDLPLIIQRLHGLSAFSLH SYSPGEINRVAACLRKLGVPPLRAWRHRARNVRARLLSRGGRAAICGKYLFNW AVRTKLKLTPIAAASQLDLSGWFVAGYGGGDIYHSLSRARPRWFWFCLLLLAA GVGIYLLPNR

Design16.mosaic3 Amino Acid Sequence SEQ ID NO: 10 MSTNPKPQRKIKRNTNRRPQDVKFPGGGKIVGGVYLLPRRGPRLGVRTTRKTS ERSQPRGRRQPIPKARQPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRGS RPNWGPTDPRRRSRNLGKVIDTLTCGLADLMGYIPLVGGPLGGAARALAHGVR VLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSSGLYHVTNDCPNS SIVYEAADAILHTPGCVPCVREGNASRCWVAMTPTVATRDGKLPTTQLRRHIDL LVGSATLCSALYVGDLCGSVFLVGQLFTFSPRRHWTTQDCNCSIYPGHITGHR MAWDMMMNWSPTTALVVAQLLRVPQAILDMIAGAHWGVLAGIAYFSMVGNWA KVLVVLLLFAGVDAETHVTGGSAAKDTSGFTSLFRIGARQNIQLINTNGSWHINR TALNCNASLDTGWVAGLFYYHKFNSSGCPERLASCRPLADFDQGWGPISYAN GSGPDQRPYCWHYPPKPCGIVPAKSVCGPVYCFTPSPVVVGTTDRSGAPTYN WGENETDVLVLNNTRPPLGNWFGCTWMNSSGFTKVCGAPPCVIGGVGNNTL HCPTDCFRKHPEATYSRCGSGPWITPRCLVNYPYRLWHYPCTVNYTLFKVRM YVGGVEHRLDAACNWTRGERCDLDDRDRSELSPLLLSTTQWQVLPCSFTSLP ALSTGLIHLHQNIVDVQYLYGVGSSIASWAIKWEYVVLLFLLLADARVCSCLWM MLLISQAEAALENLVILNAASLAGTHGLVSFLVFFCFAWYLKGRWVPGAVYALY GMWPLLLLLLALPQRAYALDTEVAASCGGWLVGLMALTLSPYYKHYISWCLW WLQYFLTRVEAHLHVWVPPLDVRGGRDAVILLMCVVHPTLVFDITKLLLAVFGP LWILQASLLKVPYFVRVQGLLRICALARKMAGGHYVQMAIIKLGALTGTYIYNHLT PLRDWAHNGLRDLAVAVEPVVFSQMETKLITWGADTAACGDIINGLPVSARRG QEILLGPADGMVSKGWRLLAPITAYSQQTRGLLGCIVTSLTGRDKNQAEGEVQI VSTAAQTFLATCINGVCWTVYHGAGTRTIASPKGPVIQMYTNVDKDLVGWPAP QGARSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGGLLSPRPISYLKGSSGG PLLCPAGHAVGIFRAAVCTRGVAKAVDFIPVENLETTMRSPVFTDNSSPPVVPQ SFQVAHLHAPTGSGKSTRVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGI DPNIRTGVRTITTGGPITYSTYCKFLADGGCSGGAYDIIICDECHSTDATSILGIGT ALDQAETAGARLVVLATATPPGSVTVSHPNIEEVALSTTGEIPFYGKAIPLEVIKG GRHLIFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGNVVVVATDALMT GFTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKP GIYRFVAPGERPSGMFDSSILCECYDAGCAVVYELTPAETTVRLRAYMNTPGLP VCQDHLEFWEGVFTGLTHIDAHFLSQTKQSGENLPYLVAYQATVCARAQAPPP SWDQMWKCLIRLKPTLHGSTPLLYRLGAVQNEVTLTHPVTKYIMTCMSADLEV VTSTWVLVGGVLAALAAYCLSTGCVVIVGRIVLSGKPAIIPDREVLYQEFDEMEE CSQQLPYIEQGMMLAEQFKQKAFGLLQTASRQAEVIAPAVQTNWQKLEAFWA KHMWNFVSGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTSQTLLFNILGGWLA AQLAAPGAATTFVGAGLAGAAIGSVGLGKVLVDILAGYGAGVAGALVAFKIMSG EAPSTEDLINLLPAILSPGALWGWCAAVLRRHVGPGEGAVQWMNRLIAFASR GNHVSPTHYVPESDAAARVTTILSSLTVTQLLRRLHQWISSECTTPCSGSWLKD VWDWICTVLSDFKTWLQSKLLPRLPGLPFLSCQRGYKGVWRGDGIMQTTCPC GAQIAGHVKNGSMRIVGPRTCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWR VAAEEYVEVTRVGDFHYVTGMTTDNVKCPCQVPAPEFFTEVDGVRLHRYAPA CKPLLREEVTFQVGLNQYLVGSQLPCEPEPDVTWTSMLTDPSHITAETAKRRL ARGSPPSLASSSASQLSAPSLKATCTTRHDSPDADLVEANLLWRQEMGGNITR VESENKWILDSFEPLRAEEDEREVSVPAEILRKTRKFPPALPIWARPDYNPPLL ESWKDPDYVPPWHGCPLPPTKAPPIPPPRRKRTWLSESTVSSALAELATKTF GSSESSAVDSGTATAPPDQASDDGDKGSDVESYSSMPPLEGEPGDPDLSDGS WSTVSEEAGEDWCCSMSYTWTGALITPCAAEESKLPINPLSNSLLRHHSMVY STTSRSASLRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSIEEACKLT PPHSAKSKYGYGAKDVRNLSSRAVNHIRSVWEDLLEDTETPIDTTIMAKSEVFC VQPEKGGRKPARLIVFPDLGVRVCEKMALYDWSTLPQAVMGSSYGFQYSPK QRVEFLVNTWKSKKCPMGFSYDTRCFDSTVTESDIRVEESIYQCCDLAPEARQ AIKSLTERLYIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKATAACRA AKLRDCTMLVNGDDLWICESAGTQEDAANLRVFTEAMTRYSAPPGDPPRPEY DLELITSCSSNVSVAHDASGKRVYYLTRDPTTPIARAAWETARSTPVNSWLGNII MYAPTLWARMVLMTHFFSILIAQEQLEKALDCQIYGACYSIEPLDLPQIIERLHGL SAFSLHSYSPGEINRVAACLRKLGVPPLRAWRHRARSVRAKLLSRGGRAAICG RYLFNWAVKTKLKLTPIAAAGQLDLSGWFTAGYSGGDIYHSVSHARPRWFWFC LLLLTAGVGIYLLPNR

Design16.mosaic4 Amino Acid Sequence SEQ ID NO: 11 MSTNPKPQRRTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPKLGVRATRKT SERSQPRGRRQPIPKARRPEGRAWAQPGYPWPLYGNEGLGWAGWLLSPRG SRPSWGPTDPRRRSRNLGRVIDTLTCGFADLMGYIPFVGAPLGGAARALAHGV RVLEDSVNYATGNLPGCSFSIFLLALLSCLTTPASAYEVRNVSGVYHVTNDCSN ASIVYEAADMIMHTPGCVPCVRENNSSRCWVALTPTLAARNASVPTTTIRRHVD LLVGAAALCSAMYVGDLCGSVFLVAQLFTFSPRRHETVQDCNCSIYPGHVTGH RMAWDMMMNWSPTAALVVSQLLRIPQAVMDMVAGAHWGILAGLAYYSMAGN WAKVLLVLLLFAGVDGNTRVSGGEAAKNTMGFASLFVSGPSQKIQLINTNGSW HINSTALNCNDSLQTGFLAALFYTHKFNSSGCPERMASCRSIDKFDQGWGPITY AEPGSSDQRPYCWHYAPKPCGIVPASQVCGPVYCFTPSPWVGTTDRFGAPT YTWGENETDVLILNNTRPPQGNWFGCTWMNGTGFTKTCGAPPCNIGGVGNNT LTCPTDCFRKHPDATYTKCGSGPWLTPRCMVDYPYRLWHYPCTVNFTIFKVR MYVGGVEHRLSAACNWTRGERCNLEDRDRSELSPLLLTTTQWQVLPCSFTTL PALTTGLIHLHQNVVDVQYLYGVGSSIVSWAIKWEYVILLFLLLADARICSCLWM MLLISQVEAALENLVLLNAASLAGTHGLASFLVFFCFAWYLKGKWVPGAVYAFY GMWPLLLLLLALPQRAYALDTEMAASCGGAVFVGLALLTLSPYYKRYISWCLW WLQYFLTRVEAQLHVWVPPLNVRGGRDAIILLTCAVHPELIFEITKILLAIIGPLMV LQAGLTRVPYFVRAQGLIRVCMLVRKAAGGHYVQMAIIKLGALTGTYVYNHLTP LRDWAHTGLRDLAVAVEPVVFSDMETKVITWGADTAACGDIILGLPVSARRGRE ILLGPADSLEGRGWRLLAPITAYAQQTRGLFGCIITSLTGRDRNQVEGEVQVVS TATQSFLATCINGVCWTVYHGAGSKTLAGPKGPVTQMYTNVDQDLVGWQAPP GARSLTPCTCGSSDLYLVTRHADVIPVRRRGDGRGSLLSPRPVSYLKGSSGGP LLCPSGHAVGIFRAAVCTRGVAKAVDFIPVESLETTMRSPVFTDNSSPPAVPQS FQVAYLHAPTGSGKSTKVPAAYAAQGYTVLVLNPSVAATLGFGAYMSKAHGVD PNIRTGVRTITTGASITYSTYGKFLADGGCSGGAYDVIICDECHSTDATTILGVGT VLDQAETAGARLVVLATATPPGSVTVPHSNIEEVALSNTGEVPFYGKAIPIETIKG GRHLIFCHSKKKCDELAAKLSGLGLNAVAYYRGLDVSVIPASGDVVVVATDALM TGYTGDFDSVIDCNTCVTQSVDFSLDPTFTIETITLPQDAVSRSQRRGRTGRGR RGIYRFVTPGERPSGMFDSVVLCECYDAGCAWYELTPAETSVRLRAYLNTPGL PVCQDHLEFWESVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARAKAPP PSWDQMWKCLVRLKPTLHGPTPLLYRLGAVQNEVILTHPITKYIMACMSADLEV VTSTWVLVGGVLAALAAYCLTTGCVVIVGRVVLSGKPAIIPDREILYREFDEMEE CSQHLPYIEQGMALAEQFKQKALGLLQTASRQAEVITPAVQTNWQKLEVFWAK HMWNFISGVQYLAGLSTLPGNPAIASLMAFTASVTSPLTTQNTLLFNILGGWVA AQLAPPSAASAFVGAGIAGAAIGSIGLGKVLVDVLAGYGAGVAGALVAFKVMSG EMPSTEDLVNLLPAILSPGALVVGVVCAAILRRHVGPGEGAVQWMNRLIAFASR GNHVSPTHYVPESDAAARVTQILSSLTITQLLKRLHQWISEDCSTPCSGSWLRDI WDWICTVLTDFKTWLQSKLLPRLPGVPFLSCQRGYRGVWRGDGIMHTTCPCG AQITGHVKNGSMRIVGPKTCSNTWHGTFPINAHTTGPCTPSPAPNYSKALWRV AAEEYVEVRRVGDFHYVTGMTTDNIKCPCQVPAPEFFTELDGVRLHRYAPACK PLLRDEVTFQVGLNQYWGSQLPCEPEPDVTVLTSMLTDPPHITAEAARRRLAR GSPPSMASSSASQLSAPSLKATCTTHHDSPDADLIEANLLWRQEMGGNITRVE SENKVVILDSFDPLRAEEDEREVSVAAEILRKSRRFAPALPIWARPDYNPPLLET WKKPDYEPPWHGCPLPPPQSPPVPPPRKKRMVVLTESTVSSALAELATKTFG SSGSSAVDSGTATAPPDQPSDDGDAGSDVESYSSMPPLEGEPGDPDLSDGS WSTVSEEASEDVVCCSMSYTWTGAMITPCAAEESKLPINALSNPLLRHHNMVY ATTSRSASQRQKKVTFDRLQVLDDHYQDVLKEMKAKASTVKAKLLSVEEACKL TPPHSARSKFGYGAKDVRSLSSKAVNHIRSVWKDLLEDTETPIDTTVMAKNEVF CIQPEKGGRKPARFIVFPDLGVRVCEKMALYDWSTLPQAVMGPSYGFQYSPG QRVEFLVNAWKSKKCPMGFAYDTRCFDSTVTENDIRVEESIYQSCDLAPEARQ AIRSLTERLYVGGPLTNSKGQSCGYRRCRASGVLTTSCGNTLTCYLKASAACR AAKLQDCTMLVNGDDLVVICESAGTQEDAASLRVFTEAMTRYSAPPGDPPKPE YDLELITSCSSNVSVAHDATGKRVYYLTRDPTTPLARAAWETARHTPVNSWLG NIIMYAPTLWVRMILMTHFFSILLAQEQLEKALDCQIYGATYSIEPLDLPQIIQRLH GLSAFSLHSYSPGEINRVATCLRKLGVPPLRVWRHRARSVRAKLLSQGGRAAT CGRYLFNWAVRTKLKLTPIPAASQLDLSSWFVAGYSGGDIYHSLSRARPRWFM WCLLLLSVGVGIYLLPNR

Design17.mosaic1 Amino Acid Sequence SEQ ID NO: 12 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRG SRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGV RVLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSTGLYHVTNDCPN SSIVYEAADAILHTPGCVPCVREGNASRCWVAVTPTVATRDGKLPTTQLRRHID LLVGSATLCSALYVGDLCGSVFLVGQLFTFSPRRHWTTQDCNCSIYPGHITGHR MAWDMMMNWSPTTALVVAQLLRIPQAILDMIAGAHWGVLAGIAYFSMVGNWA KVLVVLLLFAGVDAETHVTGGSAAKDTSGFTSLFRIGARQNIQLINTNGSWHINR TALNCNASLDTGWVAGLFYYHKFNSSGCPERMASCRSLADFDQGWGPISYAN GSGPEHRPYCWHYPPKPCGIVPAKSVCGPVYCFTPSPVVVGTTDRSGAPTYN WGENDTDVFVLNNTRPPLGNWFGCTWMNSTGFTKVCGAPPCVIGGVGNNTL HCPTDCFRKHPEATYSRCGSGPWITPRCLVNYPYRLWHYPCTINYTIFKVRMY VGGVEHRLEAACNWTRGERCDLEDRDRSELSPLLLSTTQWQVLPCSFTTLPAL STGLIHLHQNIVDVQYLYGVGSSIASWAIKWEYVVLLFLLLADARVCSCLWMMLL ISQAEAALENLVILNAASLAGTHGLVSFLVFFCFAWYLKGRWVPGAVYALYGM WPLLLLLLALPQRAYALDTEVAASCGGVVLVGLMALTLSPYYKRYISWCLWWL QYFLTRVEAQLHVWVPPLNVRGGRDAVILLMCVVHPTLVFDITKLLLAVFGPLWI LQASLLKVPYFVRVQGLLRICALARKMAGGHYVQMAIIKLGALTGTYVYNHLTPL RDWAHNGLRDLAVAVEPWFSQMETKLITWGADTAACGDIINGLPVSARRGREI LLGPADGMVSKGWRLLAPITAYAQQTRGLLGCIITSLTGRDKNQVEGEVQIVST AAQTFLATCINGVCWTVYHGAGTRTIASPKGPVIQMYTNVDQDLVGWPAPQGA RSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPLLC PAGHAVGIFRAAVCTRGVAKAVDFIPVENLETTMRSPVFTDNSSPPAVPQSFQV AHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIR TGVRTITTGSPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGTVLDQ AETAGARLVVLATATPPGSVTVPHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHL IFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTG DFDSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKPGIYR FVAPGERPSGMFDSSVLCECYDAGCAWYELTPAETTVRLRAYMNTPGLPVCQ DHLEFWEGVFTGLTHIDAHFLSQTKQSGENFPYLVAYQATVCARAQAPPPSWD QMWKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMTCMSADLEWTST WVLVGGVLAALAAYCLSTGCVVIVGRIVLSGKPAIIPDREVLYREFDEMEECSQH LPYIEQGMMLAEQFKQKALGLLQTASRQAEVIAPAVQTNWQKLEAFWAKHMW NFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTSQTLLFNILGGWVAAQLAA PGAATAFVGAGLAGAAIGSVGLGKVLVDILAGYGAGVAGALVAFKIMSGEVPST EDLVNLLPAILSPGALVVGVVCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVS PTHYVPESDAAARVTAILSSLTVTQLLRRLHQWISSECTTPCSGSWLRDIWDWI CEVLSDFKTWLKAKLMPQLPGIPFVSCQRGYRGVWRGDGIMHTRCHCGAEIT GHVKNGTMRIVGPRTCRNMWSGTFPINAYTTGPCTPLPAPNYTFALWRVSAEE YVEIRQVGDFHYVTGMTTDNLKCPCQVPSPEFFTELDGVRLHRFAPPCKPLLR EEVSFRVGLHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAGRRLARGSP PSVASSSASQLSAPSLKATCTANHDSPDAELIEANLLWRQEMGGNITRVESENK WILDSFDPLVAEEDEREISVPAEILRKSRRFAPALPIWARPDYNPPLLETWKKP DYEPPVVHGCPLPPPQSPPVPPPRKKRTVVLTESTVSTALAELATKSFGSSSTS GITGDNTTTSSEPAPSGCPPDSDAESYSSMPPLEGEPGDPDLSDGSWSTVSS GADTEDVVCCSMSYSWTGALVTPCAAEEQKLPINALSNSLLRHHNLVYSTTSR SACQRQKKVTFDRLQVLDSHYQDVLKEVKAAASKVKANLLSVEEACSLTPPHS AKSKFGYGAKDVRCHARKAVNHINSVWKDLLEDSVTPIDTTIMAKNEVFCVQPE KGGRKPARLIVFPDLGVRVCEKMALYDWSKLPLAVMGSSYGFQYSPGQRVEF LVQAWKSKKTPMGFSYDTRCFDSTVTESDIRTEEAIYQCCDLDPQARVAIKSLT ERLYVGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKARAACRAAGLQD CTMLVCGDDLVVICESAGVQEDAASLRAFTEAMTRYSAPPGDPPQPEYDLELIT SCSSNVSVAHDGAGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMFAP TLWARMILMTHFFSVLIARDQLEQALDCEIYGACYSIEPLDLPPIIQRLHGLSAFS LHSYSPGEINRVAACLRKLGVPPLRAWRHRARSVRARLLSRGGRAAICGKYLF NWAVRTKLKLTPIAAAGQLDLSGWFTAGYSGGDIYHSVSHARPRWFWFCLLLL AAGVGIYLLPNR

Design18.mosaic1 Amino Acid Sequence SEQ ID NO 13 MSTIPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRTTRKTS ERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNESCGWAGWLLSPRGS RPSWGPSDPRRRSRNLGKVIDTLTCGLADLMGYIPLVGAPLGGAARALAHGVR VLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSTGLYHVTNDCPNS SIVYETADTILHSPGCVPCVREGNASRCWVAMTPTVATRDGRLPTTQLRRHIDL LVGGATLCSALYVGDLCGSIFLVGQLFTFSPRRHWTTQGCNCSIYPGHITGHRM AWDMMMNWSPTTALWAQLLRVPQAILDMIAGAHWGVLAGMAYFSMVGNWA KVLVVLLLFAGVDAGTHVTGGSAAKDTSGFTSLFRIGARQNIQLINTNGSWHINS TALNCNDSLNTGWIAGLFYHHKFNSSGCPERLASCRPLTDFDQGWGPISHANG SGPDQRPYCWHYPPRPCGIVPAKSVCGPVYCFTPSPWVGTTDRSGAPTYNW GENDTDVFVLNNTRPPLGNWFGCTWMNSTGFTKVCGAPPCAIGGVGNNTLRC PTDCFRKHPEATYSRCGSGPWITPRCLVNYPYRLWHYPCTINYTIFKVRMYVG GVEHRLEAACNWTRGERCDLEDRDRSELSPLLLSTTQWQILPCSFTTLPALST GLIHLHQNIVDVQYLYGVGSSIASWAIKWEYVVLLFLLLADARVCSCLWMMLLIS QVEAALENLVILNAASLAGTHGLVSFLVFFCFAWYLKGRWVPGAVYALYGMWP LLLLLLALPQRAYALDTEVAASCGGVVLAGLMALTLSPHYKRYISWCMWWLQY FLTRAEAQLHVWVPPLNVRGGRDAVILLMCWHPTLVFDITKLLLAIFGPLWILQ ASLLKVPYFVRVQGLLRICALARKMVGGHYVQMAIIKLGALTGTYIYNHLTPLRD WAHNGLRDLAVAVEPVVFSRMETKLITWGADTAACGDIINGLPVSARRGQEILL GPADGMVSKGWRLLAPITAYAQQTRGLLGCIITSLTGRDKNQAEGEVQIVSTAT QTFLATCINGVCWTVYHGAGTRTIASPKGPVIQMYTNVDQDLVGWPAPQGSRS LTPCTCGSSDLYLVTRHADVIPVRRRGDGRGSLLSPRPISYLKGSSGGPLLCPA GHAVGLFRAAVCTRGVAKAVDFIPVENLETTMRSPVFTDNSSPPWPQSFQVA HLHAPTGSGKSTKVPAAYAAQGYTVLVLNPSVAATLSFGAYMSKAHGVDPNIR TGVRTITTGSPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGTVLDQ AETAGARLWLATATPPGSITVPHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHLI FCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGNVWVATDALMTGFTG DFDSVIDCNTCVTQTVDFSLDPTFTIETITLPQDAVSRTQRRGRTGRGKPGIYRF VTPGERPSGMFDSSVLCECYDAGCAWYELTPAETTVRLRAYMNTPGLPVCQD HLEFWEGVFTGLTHIDAHFLSQTKQSGENFPYLVAYQATVCARAQAPPPSWDQ MWKCLIRLKPTLHGSTPLLYRLGAVQNEVTLTHPITKYIMTCMSADLEIVTSTWV LVGGVLAALAAYCLSTGCVVIVGRIVLSGKPAVIPDREVLYQEFDEMEECSQHL PYIEQGMVLAEQFKQKALGLLQTASRQAEVITPAVQTNWQRLETFWAKHMWN FISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTGQTLLFNILGGWLAAQLAAP GAATAFVGAGLAGAAIGSVGLGKVLVDILAGYGAGVAGALVAFKIMSGDVPSTE DLVNLLPAILSPGALWGWCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVSP THYVQESDAAARVTAILSSLTVTQLLRRLHQWISSECTTPCSGSWLRDIWDWIC EVLSDFKTWLKAKLMPQLPGIPFVSCQRGYRGVWRGDGIMHTRCHCGAEIAG HVKNGTMRIVGPRTCRNMWSGTFPINAYTTGPCTPLPAPNYKFALWRVSAEEY VEIRRVGDFHYVTGMTADNLKCPCQVPSPEFFTELDGVRLHRFAPPCKPLLRD EVSFRVGLHEYPVGSQLPCEPEPDVSVLTSMLTDPSHITAEAAGRRLARGSPP SMASSSASQLSAPSLKATCTANHDSPDAELIEASLLWRQEMGSNITRVESENKV VILDSFDPLVAEEDEREVSVPAEILRKSRRFAQALPVWARPDYNPPLIETWKKP DYEPPVVHGCPLPPPRSPPVPPPRKKRTVVLTESTLSTALAELAAKSFGSSSTS GITGDDTTTSSEPAPSGCPPDSDAESCSSMPPLEGEPGDPDLSDGSWSTVSS GADTEDVVCCSMSYTWTGALVTPCAAEEQKLPINALSNSLLRHHNMVYSTTSR SACQRQKKVTFDRLQVLDSHYQDVLKEVKAAASKVKANLLSVEEACSLTPPHS AKSKFGYGAKDVRCHARKAVAHINSVWKDLLEDSVTPIDTTIMAKNEVFCVQPE KGGRKPARLIVFPDLGVRVCEKMALYDWSKLPVAVMGSSYGFQYSPGQRVEF LVQAWKSKKTPMGFSYDTRCFDSTVTENDIRTEEAIYQCCDLDPQARVAIKSLT ERLYVGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKARAACRAAGLQD CTMLVCGDDLVVICESAGVQEDAASLRAFTEAMTRYSAPPGDPPQPEYDLELIT SCSSNVSVAHDGAGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMFAP TLWARMILMTHFFSVLIARDQLEQALNCEIYGACYSIEPLDLPLIIQRLHGLSAFSL HSYSPGEINRVAACLRKLGVPPLRAWRHRARSVRAKLLSRGGRAAICGKYLFN WAVRTKLKLTPIAAAGRLDLSGWFTAGYSGGDIYHSVSHARPRWFWFCLLLLA AGVGIYLLPNR

Design18.mosaic2 Amino Acid Sequence SEQ ID NO: 14 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERSQPRGRRQPIPKARRPEGRSWAQPGYPWPLYGNEGCGWAGWLLSPRG SRPSWGPTDPRRRSRNLGRVIDTLTCGFADLMGYIPLVGAPLGGVARALAHGV RVLEDSVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSSGLYHVTNDCPN SSIVYEAADAILHTPGCVPCVREGNTSRCWVAVTPTVATRDGKLPTTQLRRHID LLVGSATLCSALYVGDLCGSVFLVGQLFTFSPRRHWTTQDCNCSIYPGHITGHR MAWDMMMNWSPTAALVVAQLLRIPQAILDMIAGAHWGVLAGIAYFSMVGNWA KVLLVLLLFAGVDAETHVTGGSAAKDTSGFTSLFRIGARQNIQLINSNGSWHINR TALNCNASLDTGWVAGLFYYHKFNSSGCPERMASCRPLTDFAQGWGPISYAN GSGPEHRPYCWHYPPKPCGIVPAQNVCGPVYCFTPSPVWGTTDKSGAPTYN WGSNDTDVLVLNNTRPPSGNWFGCTWMNSSGFTKVCGAPPCVIGGVGNNTL HCPTDCFRKHPDATYSRCGSGPWLTPRCLVDYPYRLWHYPCTVNYTLFKVRM YVGGVEHRLEVACNWTRGERCDLDDRDRSELSPLLLSTTQWQVLPCSFTTLP ALTTGLIHLHQNIVDVQYLYGVGSSIVSWAIKWEYVILLFLLLADARICSCLWMML LISQAEAALENLWLNAASLAGTHGLASFLVFFCFAWYLKGKWVPGAAYAFYG MWPLLLLLLALPQRAYALDTEMAASCGGWLVGLMALTLSPYYKRYISWCLWW LQYFLTRVEAQLHVWVPPLNVRGGRDAVILLTCWHPALVFDITKLLLAVFGPLW ILQTSLLKVPYFVRVQGLLRLCALARKMAGGHYVQMVIIKLGALTGTYVYNHLTP LRDWAHNGLQDLAVAVEPVVFSQMETKLITWGADTAACGDIIDGLPVSARRGR EILLGPADGMDSKGWRLLAPITAYAQQTRGLLGCIVTSLTGRDKNQVEGEVQIV STAAQTFLATCINGVCWTVYHGAGTRTIASSKGPVIQMYTNVDKDLVGWPAPQ GARSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPL LCPAGHAVGIFRAAVCTRGVAKAVDFIPVESLETTMRSPVFTDNSSPPAVPQSF QVAYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDP NIRTGVRTITTGSSITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSVLGIGTV LDQAETAGVRLTVLATATPPGSVTVPHPNIEEAALSTTGEIPFYGKAIPLEAIKGG RHLIFCHSKRKCDELAAKLVALGVNAVAYYRGLDVSVIPTSGDVVVVATDALMT GYTGDFDSVIDCNTCVTQSVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKP GIYRFVAPGERPSGMFDSSILCECYDAGCAWYELTPAETTVRLRSYMNTPGLP VCQDHLEFWEGVFTGLTHIDAHFLSQTKQSGENLPYLVAYQATVCARAQALPP SWDQMWKCLTRLKPTLHGPTPLLYRLGAVQNEITLTHPVTKYIMTCMSADLEVV TSTWVLVGGVLAALTAYCLSTGCVVIVGRVVLSGKPAIIPDREVLYREFDEMEE CSQHLPYIEQGMMLAEQFKQKAFGLLQTASRQAEVIAPAVQTNWQKLEAFWAK HMWNFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTSQTLLFNILGGWVAA QLAAPGAATSFVGAGLAGAAVGSVGLGKVLIDILAGYGAGVAGALVAFKIMSGE VPSTEDLVNLLPAILSPGALVVGWCAAILRRHVGPGEGAVQWMNRLIAFASRG NHVSPTHYVPESDAAARVTTILSSLTVTQLLRRLHQWVSSESTTPCSGSWLRD VWDWICEVLSDFKIWLKAKLMPQLPGIPFVSCQRGYKGVWRGDGVMHTRCHC GAEITGHVKNGTMRIVGPKTCRNMWSGTFPINAYTTGPSTPLPAPNYTFALWR VSAEEYVEIRQVGDFHYVTGMTTDNLKCPCQVPSPEFFTELDGVRLHRYAPPC KPLLREEVSFRVGLHDYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAARRRLA RGSPPSVASSSASQLSAPSLKATCTTNHDSPDAELIEANLLWRQEMGGNITRV ESENKVWLDSFDPLVAEEDEREISVPAEILRKSRRFAPALPIWARPDYNPPLLE TWKKPDYEPPWHGCPLPPPQSPPVPPPRRKRTWLTESTVSTALAELATKSF GSSSTSGITGDNTTTSSEPASSGCPPDSDAESYSSMPPLEGEPGDPDLSDGS WSTVSSEAGTEDWCCSMSYSWTGALITPCAAEEQKLPINALSNSLLRHHNLVY STTSRSACLRQKKVTFDRLQVLDNHYQDVLKEVKAAASTVKANLLSVEEACSLT PPHSARSKFGYGAKDVRCHARKAVNHINSVWKDLLEDNVTPIDTTIMAKNEVFC VQPEKGGRKPARLIVYPDLGVRVCEKMALYDWSKLPLAVMGSSYGFQYSPAQ RVEFLVQAWKSKRTPMGFSYDTRCFDSTVTESDIRTEEAIYQCCDLDPQARVAI KSLTERLYVGGPLTNSKGENCGYRRCRASGVLTTSCGNTLTCYIKAQAACRAA GLRDCTMLVCGDDLVVICESQGVQEDAANLRAFTEAMTRYSAPPGDPPQPEY DLELITSCSSNVSVAHDGTGKRVYYLTRDPTTPLARAAWETARHTPINSWLGNII MFAPTLWVRMILLTHFFSVLIARDQLEQALDCEIYGACYSIEPLDLPPIIQRLHGL SAFSLHSYSPGEINRVATCLRKLGVPPLRTWRHRARSVRARLLSRGGRAAICG RYLFNWAVKTKLKLTPIAAAGQLDLSGWFTAGYSGGDIYHSVSRARPRWFWFC LLLLTAGVGIYLLPNR

Design19.mosaic1 Amino Acid Sequence SEQ ID NO: 15 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVCATRKT SERSQPRGRRQPIPKARRSEGRTWAQPGFPWPLYGNEGCGWAGWLLSPRG SRPNWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGVARALAHGV RVLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSSGLYHVTNDCPN SSIVYETADTILHSPGCVPCVREGNASKCWVAVAPTVATRDGRLPTTQLRRHID LLVGSATLCSALYVGDLCGSIFLVGQLFTFSPRRHWTTQDCNCSMYPGHITGH RMAWDMMMNWSPTTALVMAQLLRIPQAILDMIAGAHWGVLAGMAYFSMVGN WAKVLVVLLLFAGVDAETHVTGGSAAKDTSGFTSLFRIGARQNIQLINSNGSWH INRTALNCNASLDTGWVAGLFYYHKFNSSGCPERMASCRPLADFDQGWGPIS YANGSGPEHRPYCWHYPPKPCGIVPAQSVCGPVYCFTPSPVWGTTDRSGAP TYSWGENDTDVLVLNNTRPPSGNWFGCTWMNSTGYTKVCGAPPCAIGGVGN NTLRCPTDCFRKHPEATYARCGSGPWITPRCLVHYPYRLWHYPCTVNYTLFKV RMYVGGVEHRLEVACNWTRGERCDLDDRDRSELSPLLLSTTQWQVLPCSFTT LPALTTGLIHLHQNIVDVQYLYGVGSSIVSWAIKWEYVILLFLLLADARICSCLWM MLLISQAEAALENLVLLNAASLAGMHGLASFLVFFCFAWYLKGRWVPGAAYALY GMWPLLLLLLALPQRAYALDTEMAASCGGWLVGLMALTLSPYYKHYISWCLW WLQYLLTRAEAQLHVWVPPLDARGGRDAVILLTCWHPTLIFDITKLLLAVLGPL WILQASLLKVPYFVRVQGLLRICALARKMVGGHYVQMAIIKLGALTGTYVYNHLT PLRDWAHNSLQDLAVAVEPVVFSQMETKLITWGADAAACGDIINGLPVSARRG QEILLGPADGMVSKGWRLLAPITAYAQQTRGLLGCIITSLTGRDKNQAEGEVQIV STATQTFLATCINGVCWSIYHGAGTRTIASPKGPVIQMYTNVDKDLVGWPAPQG TRSLTPCACGSSDLYLVTRHADVIPVHRRGDSRGSLLSPRPISYLKGSSGGPLL CPAGHAVGIFRAAVCTRGVAKAVDFIPVENLETTMRSPVFTDNSSPPAVPQSFQ VAYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLSFGAYMSKAHGVEPN IRTGVRTITTGSPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGTVLD QAETAGARLTVLATATPPGSVTVPHPNIEEVGLSTTGEIPFYGKAIPLEAIKGGR HLIFCHSKKKCDELAAKLVALGVNAVAYYRGLDVSIIPTSGDVVVVATDALMTGF TGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKPGI YRFVAPGERPSGMFDSSILCECYDAGCAWYELTPAETTVRLRSYMNTPGLPVC QDHLEFWEGVFTGLTHIDAHFLSQTKQGGENFPYLVAYQATVCARAQAPPPS WDQMWKCLVRLKPTLHGPTPLLYRLGAVQNEITLTHPITKYIMTCMSADLEIVTS TWVLVGGVLAALAAYCLSTGCVVIVGRIVLSGKPAVIPDREVLYREFDEMEECS QHLPYIEHGMMLAEQFKQKALGLLQTASRQAEVITPWQTNWQKLEAFWAKHM WNFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTSQTLLFNVLGGWVAAQL AAPGAATSFVGAGLAGAAVGSVGLGKVLVDIIAGYGAGVAGALVAFKIMSGEVP STEDLVNLLPAILSPGALVVGVVCAAILRRHVGPGEGAVQWMNRLIAFASRGNH VSPTHYVPESDAAARVTNILSSLTVTQLLRRLHQWVSSECTTPCSDSWLRDIW DWICEVLSDFKTWLKAKLVPQLPGIPFVSCQRGYKGVWRGDGVMHTRCHCGA EIAGHVKNGTMRIVGPKTCRNMWSGTFPINAYTTGPSTPLPAPNYTFALWRVS AEEYVEVRQVGDFHYVTGMTTDNLKCPCQVPSPEFFTELDGVRIHRFAPPCKP LLRDEVSFRVGLHDYPVGSQLPCEPEPDVTVVTSMLTDPSHITAEAAGRRLAR GSPPSVASSSASQLSAPSLKATCTANHDSPDAELIEASLLWRQEMGSNITRVES ENKVVVLDSFDPLVAEEDEREVSVPAEILRKSRRFTPALPIWARPDYNPPLLET WKKPDYEPPWHGCPLPPPRSPPVPPPRRKRTWLTESSVSTALAELATKSFG SSSTSGITGDDTTTPSEPAPSACPPDSDAESCSSMPPLEGEPGDPDLSDGSWS TVSSGADTEDVVCCSMSYSWTGALITPCAAEEQKLPINALSNSLLRHHNLVYST TSRSACLRQKKVTFDRLQVLDSYYQDVLKEVKAAASTVKANLLSVEEACSLTPP HSARSKFGYGAKDVRSHARKAVNHINSVWEDLLEDNVTPIDTTIMAKNEVFCVQ PEKGGRKPARLIVFPDLGVRVCEKRALYDVVSKLPVAVMGSSYGFQYSPGQRV EFLVQAWKSKKTPMGFSYDTRCFDSTVTESDIRTEEAIYQCCDLDPQARVVIKS LTERLYVGGPLTNSKGENCGYRRCRASGVLTTSCGNTLTCYIKAKAACRAAGL RDCTMLVCGDDLVVICESQGVQEDAASLRAFTEAMTRYSAPPGDPPQPEYDLE LITSCSSNVSVAHDGTGKRVYYLTRDPTTPLARAAWETARHTPINSWLGNIIMFA PTLWARMILMTHFFSVLIARDQLEQALDCEIYGACYSIEPLDLPLIIQRLHGLSAF SLHSYSPGEINRVAACLRKLGVPPLRAWRHRARSVRARLLSRGGKAAICGKYL FNWAVRTKLKLTPIAAASQLDLSGWFTAGYSGGDIYHSVSRARPRWIWFCLLLL TAGVGIYLLPNR

Design19.mosaic2 Amino Acid Sequence SEQ ID NO: 16 MSTNPKPQRRTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRTTRKT SERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNESCGWAGWLLSPRG SRPSWGPSDPRRRSRNLGRVIDTLTCGFADLMGYIPFVGAPLGGAARALAHGV RVLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSSGIYHVTNDCPN SSIVYETADAILHSPGCVPCVREGNTSRCWVAMTPTVATRDGKLPATQLRRHID LLVGGATLCSALYVGDLCGSVFLVSQLFTFSPRRHWTTQGCNCSIYPGHITGHR MAWDMMMNWSPTAALVVAQLLRIPQAIMDMIAGAHWGVLAGIAYFSMVGNWA KVLLVLLLFAGVDAGTHVTGGSAAKDTSGFTSLFRIGARQNIQLINSNGSWHINR TALNCNESLNTGWLAGLFYQHKFNSSGCPERLASCRPLTDFAQGWGPISHAN GSGPDQRPYCWHYPPRPCGIVPAQNVCGPVYCFTPSPVWGTTNKLGAPTYN WGENETDVFVLNNTRPPLGNWFGCTWMNSTGFTKVCGAPPCVIGGVGNNTLL CPTDCFRKHPDATYSRCGSGPWITPRCLVNYPYRLWHYPCTINYTIFKVRMYV GGVEHRLDAACNWTRGERCDLEDRDRSELSPLLLTTTQWQVLPCSFTSLPALS TGLIHLHQNIVDVQYLYGVGSSIASWAIKWEYVVLLFLLLADARVCSCLWMMLLI SQVEAALENLVILNAASLAGTHGLASFLVFFCFAWHLKGRWVPGAVYALYGMW PLLLLLLALPQRAYALDTEVAASCGGAVLVGLMALTLSPYYKRYISWCMWWLQ YFLTRVEAQLHVWVPPLNVRGGRDAVILLMCWHPTLVFDITKLLLAIFGPLWIL QASLLKVPYFVRVQGLLRVCALARKMAGGHYVQMVIIKLGALTGTYIYNHLTPLR DWAHNGLQDLAVAVEPVVFSRMETKLITWGADTAACGDIINGLPVSARKGREIL LGPADGMASKGWRLLAPITAYAQQTRGLLGCIITSLTGRDKNQVEGEIQIVSTAA QTFLATCINGVCWTVYHGAGTRTIASSKGPVIQMYTNVDQDLVGWPAPQGSRS LTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPLLCPA GHAAGIFRAAVCTRGVAKAVDFIPVEGLETTMRSPVFTDNSSPPWPQSFQVA HLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGVYMSKAHGVDPNIR TGVRTITTGSPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSVLGIGTVLDQ AETAGVRLTVLATATPPGSVTVSHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHL IFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVSTDALMTGFTG DFDSVIDCNTCVTQSVDFSLDPTFTIETITLPQDAVSRTQRRGRTGRGRPGIYRF VAPGERPSGIFDSSVLCECYDAGCAWYELTPAETTVRLRAYMNTPGLPVCQDH LEFWEGVFTGLTHIDAHFLSQTKQSGENLPYLVAYQATVCARARAPPPSWDQM WKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPVTKYIMTCMSADLEWTSTWV LVGGVLAALAAYCLSTGCVVIVGRIVLSGKPAIVPDREVLYREFDEMEECSQHLP YIEQGMALAEQFKQKALGLLQTASRQAEVITPAVQTNWQKLEVFWAKHMWNFI SGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTGQTLLFNILGGWLAAQLAAPG AATAFVGAGLAGAAIGSVGLGKVLVDILAGYGAGVAGALVAFKIMSGDVPSTED LVNLLPAILSPGALVVGWCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVSPT HYVPESDAAARVTAILSSLTVTQLLRRLHQWISSECTTPCSGSWLRDVWDWIC EVLSDFKTWLKAKLMPQLPGIPFVSCQRGYRGVWQGDGIMHTRCHCGAEITG HVKNGTMRIAGPRTCRNMWSGTFPINAYTTGPCTPLPAPNYSFALWRVSAEEY VEIRRVGDFHYVSGMTTDNLKCPCQIPSPEFFTELDGVRLHRYAPPCKPLLRDE VSFRVGLHAYPVGSQLPCEPELDVAVLTSMLTDPSHITAEAARRRLARGSPPS MASSSASQLSAPSLKGTCTANHDSPDAELIEANLLWRQEMGGNITRVESENKV VILDSFEPLVAEEDEREISVPAEILRKSRRFAPALPIWARPDYNPPLVETWKKPD YEPPVVHGCPLPPPQSPPVPPPRKKRTVVLTESTLSTALAELATRSFGSSSTSG ITGDNTTTSSEPAPSGCPPDSDVESYSSMPPLEGEPGDPDLSDGSWSTVSSG ADAEDWCCSMSYSWTGALVTPCAAEEQKLPINALSNSLLRHHNMVYSTTSRS ASQRQKKVTFDRLQVLDSHYQDVLKEVKAAASKVKASLLSVEEACSLTPPHSA KSKFGYGAKDVRCHARKAVAHINSVWKDLLEDSETPIDTTIMAKNEVFCVQPEK GGRKPARLIVYPDLGVRVCEKMALYDWSKLPLAVMGSSYGFQYSPAQRVEFL VQAWKSKKNPMGFSYDTRCFDSTVTENDIRTEEAIYQCCDLDPQARVAIKSLTE RLYVGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKARAACRAAGLQDC TMLVCGDDLVVICESAGVQEDAASLRAFTEAMTRYSAPPGDPPQPEYDLELITS CSSNVSVAHDGAGKRVYYLTRDPTTPLARAAWETAKHTPVNSWLGNIIMFAPT LWARMILMTHFFGVLIARDQLEQALNCEIYGACYSIEPLDIPPIIQRLHGLSAFSLH SYSPGEINRVAACLRKLGVPPLRAWRHRARNVRARLLSRGGRAAICGKYLFNW AVKTKLKLTPIAAAGRLDLSGWFTAGYSGGDIYHSVSHARPRWFWFSLLLLAAG VGIYLLPNR

Design19.mosaic3 Amino Acid Sequence SE ID NO: 17 MSTNPKPQRQTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERSQPRGRRQPIPKARRPEGRSWAQPGYPWPLYGNEGCGWAGWLLSPRG SRPSWGPTDPRRRSRNLGKVIDTLTCGLADLMGYIPLVGAPLGGAARALAHGV RVLEDSVNYATGNLPGCSFSIFLLALLSCLTVPTSAYQVRNSTGLYHVTNDCPN SSIVYEAADAILHTPGCVPCVREGNASRCWVAVTPTVATRDGKLPTTQLRRHID LLVGSATLCSALYVGDLCGSVFLVGQLFTFSPRHHWTTQDCNCSIYPGHITGHR MAWDMMMNWSPTTALVVAQLLRVPQAILDMIAGAHWGVLAGLAYFSMVGNW AKVIWLLLFAGVDAGTHVTGGSAAKDTSGFTSLFRIGARQNIQLINTNGSWHIN STALNCNDSLNTGWIAGLFYHHKFNSSGCSERLASCRPLTDFDQGWGPISYTN GSGPDHRPYCWHYPPKPCGIVPAKSVCGPVYCFTPSPVVVGTTDKSGAPTYN WGENDTDVFVLNNTRPPLGNWFGCTWMNSSGFTKVCGAPPCVIGGVGNNTL HCPTDCFRKHPEATYSRCGSGPWLTPRCLVDYPYRLWHYPCTINYTIFKIRMYV GGVEHRLEAACNWTRGERCNLDDRDRSELSPLLLSTTQWQILPCSFTTLPALS TGLIHLHQNVVDVQYLYGVGSSIASWAIKWDYVVLLFLLLADARVCSCLWMMLL ISQAEAALENLVVLNAASLAGTHGLVSFLVFFCFAWYLKGKWVPGAVYAFYGM WPLLLLLLALPQRAYAQDTEVAASCGGWLAGLMALTLSPHYKRYISWCLWWL QYFLTRAEALLHVWVPPLNVRGGRDAIILLMCVVHPALVFDITKLLLAVFGPLWIL QTSLLKVPYFVRVQGLLRLCALVRKMAGGHYVQMAIIKVGALTGTYVYNHLTPL RDWAHNGLRDLAVAVEPWFSPMETKLITWGADTAACGDIIDGLPVSARRGREI LLGPADGVVSKGWRLLAPITAYAQQTRGLLGCIVTSLTGRDKNQVEGEVQIVST AAQTFLATCVNGVCWTVYHGAGTRTLASSKGPVIQMYTNVDQDLVGWPAPQG ARSLTPCTCGSSDLYLVTRHADVIPVRRRGDGRGSLLSPRPISYLKGSSGGPLL CPAGHAVGLFRAAVCTRGVAKAVDFIPVESLETTMRSPVFSDNSSPPAVPQCY QVAHLHAPTGSGKSTKVPAAYAAQGYTVLVLNPSVAATLGFGAYMSKAHGIDP NIRTGVRTITTGSSITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGTAL DQAETAGARLVVLATATPPGSITVPHPNIEEVALSTTGEIPFYGKAIPLETIKGGR HLIFCHSKKKCDELAAKLTALGINAVAFYRGLDVSVIPASGDVWVATDALMTGY TGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKPGI YRFVTPGERPSGMFDSSVLCECYDTGCAWYELTPAETTVRLRAYMNTPGLPV CQDHLEFWEGVFTGLTHIDAHFLSQTKQSGENFPYLVAYQATVCARAQALPPS WDQMWKCLTRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMTCMSADLEWT STWVLVGGVLAALTAYCLSTGCVVIVGRVVLSGKPAIIPDREVLYQEFDEMEEC SQHLPYIEQGMMLAEQFKQKAFGLLQTASRQAEVIAPAVQTNWQRLETFWAKH MWNFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTSQTLLFNILGGWVAAQ LAAPGAATAFVGAGLTGAAIGSVGLGKVLIDILAGYGAGVAGALVAFKIMSGEVP STEDMVNLLPAILSPGALWGWCAAILRRHVGPGEGAVQWMNRLIAFASRGN HVSPTHYVPESDAAARVTTILSSLTVTQLLRRLHQWISSESTTPCSGSWLRDIW DWICEVLSDFKIWLKAKLMPQLPGIPLVSCQRGYRGVWRGDGIMHTRCHCGAE ITGHVRNGTMRIVGPRTCRNMWNGTFPINAYTTGPCTPLPAPNYKFALWRVSA EEYVEIRQVGDFHYVTGMTADNLKCPCQVPSPEFFTELDGVRLHRFAPPCKPL LREEVSFRVGLHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAETAKRRLARGS PPSEASSSASQLSAPSLKATCTTNHDSPDAELLEANLLWRQEMGGDITRVESK NKVVILDSFDPLVAEEDEREISVPAEILRKSRRFAQALPVWARPDYNPPLIETWK KPDYEPPWHGCPLPPPKSPPVPPPRRKRTVVLTESTVSTALAELATKSFGSSS TSGVTGDNTTTSSEPASSGCPPDSDAESYSSMPPLEGEPGDPDLSDGSWSTV SSEAGTEDWCCSMSYTWTGALITPCAAEEQKLPINALSNSLLRYHNLVYSTTS RSACQRQKKVTFDRLQVLDNHYQDVLKEVKAAASKVKANLLSVEEACDLTPPH SAKSKFGYGAKDVRCHARKAVNHINSVWKDLLEDSVTPIDTTIMAKNEVFCVQP EKGGRKAARLIVFPDLGVRVCEKMALYDVVSKLPQAVMGSSYGFQYSPGQRV EFLVQAWKSKRTPMGFSYDTRCFDSTVTESDIRMEEAIYQCCDLDPQARVAIR SLTERLYVGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKAQAACRAAG LQNCTMLVCGDDLVVICESEGVQEDAANLRAFTEAMTRYSAPPGDPPQPEYDL ELITSCSSNVSVAHDDAGKRVYYLTRDPTTPFARAAWETARHTPVNSWLGNIIM FAPTLWVRMIMMTHFFSVLMARDQLEQALDCEIYGACYSIEPLDLPPIIQRLHGL SAFSLHSYSPGEINRVATCLRKLGVPPLRAWRHRARSVRAKLLSRGGRAAICG RYLFNWAVRTKLNLTPIAAAGQLDLSGWFTAGYSGGDIYHSVSRARPRWFWF CLLLLAAGVGIYLFPNR

Design20.mosaic1 Amino Acid Sequence SEQ ID NO: 18 MSTNPKPQRRTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRTTRKT SERSQPRGRRQPIPKARRPEGRSWAQPGYPWPLYGNEGCGWAGWLLSPRG SRPSWGPTDPRRRSRNLGKVIDTLTCGLADLMGYIPFVGAPLGGAARALAHGV RVLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSSGIYHVTNDCPN SSIVYETADAILHSPGCVPCVREGNASRCWVAVTPTVATRDGKLPTTQLRRYID LLVGSATLCSALYVGDLCGSVFLVSQLFTFSPRRHWTTQDCNCSIYPGHVTGH RMAWDMMMNWSPTTALIVAQLLRVPQAILDMIAGAHWGVLAGIAYYSMVGNW AKVVVVLLLFAGVDAGTHVTGGSAAKDTSGFTSLFRIGARQNIQLINSNGSWHI NSTALNCNDSLNTGWIAGLFYHHKFNSSGCPERLASCRPLTDFAQGWGPISYA NGSGPDQRPYCWHYPPKPCGIVPAKSVCGPVYCFTPSPVAVGTTDRSGAPTY NWGENDTDVFVLNNTRPPLGNWFGCTWMNATGFTKVCGAPPCAIGGVGNNT LRCPTDCFRKHPEATYARCGSGPWLTPRCLVDYPYRLWHYPCTINYTIFKVRM YVGGVEHRLEVACNWTRGERCNLDDRDRSELSPLLLSTTQWQVLPCSFTPMP ALSTGLIHLHQNIVDVQYLYGVGSSIASWAIKWDYVVLLFLLLADARVCSCLWM MLLISQAEAALENLVILNAASLAGTHGLVSFLVFFCFAWYLKGRWVPGAVYAVY GMWPLLLLLLALPQRAYALDTEVAASCGGWLVGLMALTLSPYYKRYISWCMW WLQYFLTRVEAQLHVWVPPLNVRGGRDAVILLTCWHPTLVFDITKLLLAIFGPL WILQASLLKVPYFVRVQGLLRICALARKIAGGHYVQMAIIKVGALTGTYVYDHLT PLRDWAHNGLRDLAVAVEPVVFSKMETKLITWGADTAACGDIIDGLPVSARRG REVLLGPADGMVSRGWRLLAPITAYAQQTRGLLGCIITSLTGRDKNQVEGEVQI VSTATQTFLATCINGACWTVYHGAGTRTIASPKGPVIQMYTNVDKDLVGWPAP QGTRSLTPCTCGSSDLYLVTRHADVIPVCRRGDSRGSLLSPRPISYLKGSSGGP LLCPAGHAAGIFRAAVCTRGVAKAVDFIPVESLETTMRSPVFTDNSSPPVVPQS FQVAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLSFGAYMSKAHGVE PNIRTGVRTITTGSPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSVLGIGT ALDQAETAGARLWLATATPPGSVTVPHPNIEEVGLSTTGEIPFYGKAIPLETIKG GRHLIFCHSKKKCDELAAKLVGLGLNAVAYYRGLDVSVIPASGDVVVVATDALM TGYTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGK PGTYRFVAPGERPSGMFDSSVLCECYDTGCAWYELTPAETTVRLRAYMNTPG LPVCQDHLEFWEGVFTGLTHIDAHFLSQTKQSGESLPYLVAYQATVCARAQAP PPSWDQMWKCLVRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMTCMSADL EVVTSTWVLVGGVLAALAAYCLSTGCVVIVGRIVLSGKPAIIPDREVLYQEFDEM EECSQHLPYIEQGMMLAEQFKQKALGLLQTASRQAEVITPVVQTNWQKLEVFW AKHMWNFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTGQTLLFNILGGWV AAQLAAPGAATTFVGAGLAGAAIGSVGLGKVLVDIIAGYGAGVAGALVAFKIMS GEVPSTEDLVNLLPAILSPGALWGWCAAILRRHVGPGEGAVQWMNRLIAFAS RGNHVSPTHYVQESDAAARVTAILSSLTVTQLLRRLHQWVSSECTTPCSDSWL RDIWDWICEVLSDFKTWLKAKLMPQLPGIPFVSCQRGYRGVWQGDGIMHTRC PCGAEIAGHVKNGTMRIVGPKTCRNMWSGTFPINAYTTGPCTPLPAPNYKFAL WRVSAEEYVEIRRVGDFHYVTGMTTDDLKCPCQVPSPEFFTELDGVRLHRFAP PCKPLLREEVTFRVGLHDYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAARRR LARGSPPSEASSSASQLSAPSLKATCTTNHDSPDAELIEASLLWRQEMGGNITR VESENKWILDSFDPLTAEEDEREISVAAEILRKSRRFTPALPIWARPDYNPPLLE TWKKPDYEPPVVHGCPLPPPKSPPVPPPRKKRTVVLTESNLSTALAELATRSF GSSSTSGITGDNTTTSSEPAPSGCPPDSDVESYSSMPPLEGEPGDPDLSDGS WSTVSSGADTEDVVCCSMSYTWTGALVTPCAAEEQKLPINALSNSLLRHHNLV YSTTSRSACQRQKKVTFDRLQVLDSYYQDVLKEVKAAASKVKANLLSVEEACD LTPPHSAKSKFGYGAKDVRSHARKAVNHINSVWEDLLEDNVTPIDTTIMAKNEV FCVQPEKGGRKPARLIVFPDLGVRVCEKMALYDWSKLPVAVMGSSYGFQYSP GQRVEFLVQAWKSKKNPMGFSYDTRCFDSTVTESDIRMEEAIYQCCDLDPQA RVAIKSLTERLYVGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKARAAC RAAGLQNCTMLVCGDDLWICESAGVQEDAASLRAFTEAMTRYSAPPGDPPQ PEYDLELITSCSSNVSVAHDDAGKRVYYLTRDPTTPFARAAWETARHTPVNSW LGNIIMFAPTLWARMILMTHFFSVLIARDQLEQALNCEIYGACYSIEPLDLPPIIQR LHGLSAFSLHSYSPGEINRVAACLRKLGVPPLRAWRHRARSVRARLLSRGGRA ATCGKYLFNWAVKTKLKLTPIAAASRLDLSGWFTAGYSGGDIYHSVSRARPRWI WFCLLLLTAGVGIYLLPNR

Design20.mosaic2 Amino Acid Sequence SEQ ID NO: 19 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERSQPRGRRQPIPKARRPEGRTWAQPGHPWPLYGNESCGWAGWLLSPRG SRPSWGPSDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGVARALAHGV RVLEDGVNYATGNLPGCSFSIFLLALLSCLAVPASAYQVRNSSGLYHVTNDCSN SSIVYETADTILHSPGCVPCVREGNASKCWVAVAPTVATRDGRLPTTQLRRHID LLVGGATLCSALYVGDLCGSIFLVGQLFTFSPRHHWTTQGCNCSIYPGHITGHR MAWDMMMNWSPTTALVVAQLLRVPQAILDMIAGAHWGVLAGIAYFSMVGNWA KVLLVLLLFAGVDAGTHVTGGSAAKDTSGFTSLFRIGARQNIQLVNTNGSWHIN RTALNCNASLDTGWVAGLFYYHKFNSSGCPERMASCRPLADFDQGWGPISHA NGSGPDQRPYCWHYAPKPCGIVPAQSVCGPVYCFTPSPVWGTTDKSGAPTY NWGANDTDVLVLNNTRPPLGNWFGCTWMNSSGYTKVCGAPPCVIGGVGNNT LLCPTDCFRKHPEATYSRCGSGPWITPRCLVNYPYRLWHYPCTINYTVFKVRM YVGGVEHRLDAACNWTRGERCNLEDRDRSELSPLLLSTTQWQVLPCSFATLP ALSTGLIHLHQNVVDVQYLYGVGSSVASWAIKWEYVVLLFLLLADARICSCLWM MLLISQVEAALENLWLNAASLAGAHGLVSFLVFFCFAWYLKGKWVPGAVYALY GMWPLLLLLLALPQRAYAMDTEVAASCGGVVLAGLMVLTLSPYYKHYISWCLW WLQYFLTRAEAQLHVWVPPLNVRGGRDAIILLMCVVHPTLVFDITKLLLAVLGPL WILQASLLKVPYFVRVQGLLRICALARKMVGGHYVQMAIIKLGALTGTYIYNHLT PLQDWAHNGLRDLAAAVEPVVFSRMETKLITWGADTAACGDIINGLPVSARKG REILLGPADGVVSKGWRLLAPITAYAQQTRGLLGCI1TSLTGRDKNQAEGEVQIV STAAQTFLATCVNGVCWTVYHGAGTRTIASSKGPVIQMYTNVDQDLVGWPAP QGSRSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGGLLSPRPISYLKGSSGG PLLCPEGHAVGIFRAAVCTRGVAKAVDFIPVENLETTMRSPVFTDNSTPPAVPQ SYQVAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGI DPNIRTGVRTITTGSSITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGT ALDQAETAGVRLTVLATATPPGSVTVPHHNIEEVALSTTGEIPFYGKAIPLEVIKG GRHLIFCHSKKKCDELAAKLVALGVNAVAYYRGLDVSVIPTSGDVVVVATDALM TGFTGDFDSVIDCNTCVTQSVDFSLDPTFTIETITLPQDAVSRTQRRGRTGRGK PGIYRFVAPGERPSGIFDSSVLCECYDAGCAVVYELTPAETTVRLRAYMNTPGL PVCQDHLEFWEGVFTGLTHIDAHFLSQTKQGGENFPYLVAYQATVCARAQALP PSWDQMWKCLIRLKPTLHGSTPLLYRLGAVQNEVTLTHPVTKYIMTCMSADLE VVTSTWVLVGGVLAALAAYCLSTGCVVIVGRIVLSGRPAIIPDREVLYREFDEME ECSQHLPYIEQGMVLAEQFKQKALGLLQTASRQAEAITPAVQTNWQKLETFWA KHMWNFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTSQTLFFNILGGWVA AQLAAPGAATAFVGAGLAGAAIGGVGLGKVLVDILAGYGAGVAGALVAFKIMSG DVPSTEDLVNLLPAILSPGALVVGVVCAAILRRHVGPGEGAVQWMNRLIAFASR GNHVSPTHYVPESDAATRVTAILSSLTVTQLLRRLHQWISSESTTPCSGSWLRD IWDWVCEVLSDFKIWLKAKLMPQLPGVPFVSCQRGYKGVWRGDGIMHTRCHC GAEIAGHVKNGTMRIVGPRTCRNMWNGTFPINAYTTGPCTPLPAPNYEFALWR VSAEEYVEVRRVGEFHYVTGMTADNLKCPCQVPSPEFFTELDGVRLHRFAPPC KPLLRDEVSFRVGLHEYPVGSQLPCEPEPDVSVLTSMLTDPSHITAETAGRRLA RGSPPSLASSSASQLSAPSLKATCTANHDSPDAELLEANLLWRQEMGSNITRV ESENKVVILDSFEPLVAEEDEREISVPAEILRKSRRFAPALPIWARPDYNPPLLEV WKKPDYEPPVVHGCPLPPSQSPPVPPPRKKRTVVLTESTVSTALAELATKSFG SSSTSGVTGDSTTTPSEPAPSACPPDSDAESCSSMPPLEGEPGDPDLSDGSW STVSSEADAEDVVCCSMSYTWTGALITPCAAEEQKLPINALSNSLLRHHNMVYS TTSRSACHRQKKVTFDRLQVLDDHYQDVLKEVKTAASKVKANLLSVEEACSLT PPHSAKSKFGYGAKDVRCHARKAVAHINSVWKDLLEDSVTPIDTTIMAKNEVFC VQPEKGGRKPARLIVYPDLGVRVCEKMALYDVVSKLPLAVMGSSYGFQYSPG QRVEFLVQAWKSKRTPMGFSYDTRCFDSTVTESDIRTEEAIYQCCDLDPQARV AIRSLTERLYVGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKAKAACRA AGLQDCTMLVCGDDLVVICESEGVQEDAANLRAFTEAMTRYSAPPGDPPQPE YDLELITSCSSNVSVAHDGAGKRVYYLTRDPTTPLARAAWETAKHTPVNSWLG NIIMFAPTLWVRMIMMTHFFSVLLARDQLEQALDCEIYGACYSIEPLDLPLIIQRL HGLSAFSLHSYSPGEINRVATCLRKLGVPPLRAWRHRARNVRARLMSRGGRA AICGKYLFNWAVRTKLKLTPIAAASQLDLSGWFTAGYSGGDIYHSVSRARPRWF WFCLLLLAAGVGVYLLPNR

Design20.mosaic3 Amino Acid Sequence SEQ ID NO: 20 MSTIPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVCATRKTS ERSQPRGRRQPIPKARRSEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRGS RPSWGPNDPRRRSRNLGKVIDTLTCGFADLMGYIPFVGAPLGGAARALAHGVR VLEDGVNYATGNLPGCSFSIFLLALLSCLTVPTSAYQVRNSTGLYHVTNDCPNS SIVYETADAILHAPGCVPCVREGNTSRCWVAMTPTVATRDGKLPTKQLRRHIDL LVGSATLCSALYVGDLCGSVFLIGQLFTFSPRRHWTTQGCNCSMYPGHITGHR MAWDMMMNWSPTAALVVAQLLRIPQAIMDMIAGAHWGVLAGIAYFSMAGNWA KVLVVLLLFAGVDAGTHVTGGSAAKDTSGFTSLFRIGARQNIQLINTNGSWHINS TALNCNESLNTGWLAGLFYQHKFNSSGCPERLASCRRLTDFDQGWGPISYAN GSGLDERPYCWHYPPRPCGIVPAKSVCGPVYCFTPSPVVVGTTDRSGAPTYS WGANDTDVFVLNNTRPPLGNWFGCTWMNSTGFTKVCGAPPCVIGGVGNNTL YCPTDCFRKHPDATYSRCGSGPWITPRCLVDYPYRLWHYPCTINYTIFKIRMYV GGVEHRLEAACNWTRGERCDLEDRDRSELSPLLLSTTQWQILPCSFTTLPALS TGLIHLHQNIVDVQYLYGVGSSIASWAIKWEYVVLLFLLLADARVCSCLWMMLLI SQVEAALENLVLLNVASLAGTHGLASFLVFFCFAWHLKGRWVPGAAYALYGM WPLLLLLLALPQRAYALDTEMAASCGGWLVGLMVLTLSPHYKRYISWCFWWL QYFLTRVEAHLHVWVPPLDVRGGRDAVILLMCAVHPALVFDITKLLLAVFGPLWI LQTSLLRVPYFVRVQGLLRLCALARKMAGGHYVQMVIIKLGALTGTYVYNHLTP LRDWAHNGLQDLAVAVEPVVFSPMETKLITWGADTAACGDIINGLPVSARRGR EILLGPADGMVSKGWRLLAPITAYAQQTRGLLGCIVTSLTGRDKNQAEGEVQIV STAAQTFLATCINGVCWTVYHGAGTRTLASPKGPVIQMYTNVDKDLVGWPAPQ GARSLTPCACGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPL LCPAGHAVGIFRAAVCTRGVAKAVDFVPVESLETTMRSPVFTDNSSPPAVPQS FQVAHLHAPTGSGKSTKVPAAYAAQGYTVLVLNPSVAATLGFGVYMSKAHGVD PNIRTGVRTITTGSSITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGTV LDQAETAGARLTVLATATPPGSVTVSHPNIEEVALSTTGEIPFYGKAIPLDVIKGG RHLIFCHSKKKCDELAAKLTALGINAVAFYRGLDVSVIPTSGNVVVVATDALMTG YTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKPG IYRFVTPGERPSGMFDSSILCECYDAGCAWYELTPAETTVRLRSYMNTPGLPV CQDHLEFWEGVFTGLTHIDAHFLSQTKQSGENFPYLVAYQATVCARAQAPPPS WDQMWKCLNRLKPTLHGPTPLLYRLGAVQNEITLTHPITKYIMTCMSADLEIVTS TWVLVGGVLAALAAYCLSTGCVVIVGRVVLSGKPAIIPDREVLYKEFDEMEEGS QHLPYIEQGMALAEQFKQKALGLLQTASRQAEVITPAVQTNWQRLEAFWAKHM WNFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTSQTLLFNILGGWVASQL AAPGAATSFVGAGLAGAAVGSVGLGKVLIDILAGYGAGVAGALVAFKIMSGEVP STEDMVNLLPAILSPGALWGWCAAILRRHVGPGEGAVQWMNRLIAFASRGN HVSPTHYVPESDAAARVTTILSSLTVTQLLRRLHQWISSECTTPCSGSWLREIW DWICEVLSDFKTWLKAKLMPQLPGIPLVSCQRGYRGVWRGDGIMHTRCHCGA EITGHVKNGTMRIVGPRTCRNTWSGTFPINAYTTGPSTPLPAPNYTFALWRVSA EEYVEVRQVGDFHYVTGMTTDNLRCPCQVPSPEFFTELDGVRIHRFAPPCKPL LREEVSFRVGLHAYPVGSQLPCEPEPDVAWTSMLTDPSHITAEAAGRRLARG SPPSVASSSASQLSAPSLKATCTVNHDSPDADLIEANLLWRQEMGGNITRVESE NKVVVLDSFDPLVAEEDEREVSVPAEILRKSRKFTPALPIWARPDYNPPLVETW KKPDYEPPVVHGCPLPPPRSPPVPPPRRKRTWLTESSVSTALAELATKSFGSS STSGITGDNTATSSEPAPSGCSPDSDAESYSSMPPLEGEPGDPDLSDGSWST VSSEAGTEDVVCCSMSYSWTGALVTPCAAEEQKLPINALSNSLLRNHNLVYST TSRSASQRQKKVTFDRLQVLDSHYQDVLKEVKAAASKVKASLLSVEEACNLTP PHSAKSKFGYGAKDVRCHARKAVNHINSVWKDLLEDNVTPIDTTIMAKNEVFCV QPEKGGRKAARLIVFPDLGVRVCEKMALYDLVSKLPLAVMGSSYGFQYSPGQR VEFLVKAWKSKKTPMGFSYDTRCFDSTVTENDIRTEEAIYQCCDLDPQARVVIK SLTERLYVGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKAQAACRAAG LRDCTMLVCGDDLVVICESAGVQEDAAGLRAFTEAMTRYSAPPGDPPQPEYDL ELITSCSSNVSVAHDGTGKRVYYLTRDPTTPLARAAWETARHTPINSWLGNIIMF APTLWVRMILLTHFFSVLIARDQLEQALDCEIYGACYSIEPLDLPLIIQRLHGLSAF SLHSYSPGEINRVAACLRKLGVPPLRAWRHRARNVRARLLSRGGKAAICGKYL FNWAVKTKLRLTPIAAAGRLDLSGWFTAGYSGGDIYHSVSHARPRWFWFCLLL LAAGVGIYLLPNR

Design20.mosaic4 Amino Acid Sequence SEQ ID NO: 21 MSTNPKPQRQTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRG SRPNWGPTDPRRRSRNLGKVIDTLTCGLADLMGYIPLVGAPLGGAARALAHGV RVLEDSVNYATGNLPGCSFSIFLLALLSCLTVPASAHQVRNSTGLYHVTNDCPN SSIVYEAADAILHTPGCVPCVREGNVSRCWVAITPTVATRDGKLPATQLRRHIDL LVGSATLCSALYVGDLCGSVFLVGQLFTFSPRQHWTTQDCNCSMYPGHITGHR MAWDMMMNWSPTTALVMAQLLRIPQAILDMIAGAHWGVLAGMAYFSMVGNW AKVLVVLLLFAGVDAETHVTGGSAAKDTSGFTSLFRIGARQNIQLINSNGSWHIN RTALNCNESLDTGWVAGLLYYHKFNSSGCPERMASCRSLADFDQGWGPISYA NGSGPEHRPYCWHYPPKPCGIVPAQNVCGPVYCFTPSPVVVGTTDKAGAPTY NWGENETDVFVLNNTRPPLGNWFGCTWMNSSGFTKVCGAPPCNIGGVGNNT LHCPTDCFRKHPEATYARCGSGPWITPRCLVHYPYRLWHYPCTVNYTLFKVRM YVGGVEHRLDVACNWTRGERCDLDDRDRSELSPLLLTTTQWQVLPCSFTTLP ALTTGLIHLHQNIVDVQYLYGVGSSIVSWAIKWEYVILLFLLLADARICSCLWMML LISQAEAALENLVLLNAASLAGMHGLASFLVFFCFAWYLKGKWVPGAAYAFYG MWPLLLLLLALPQRAYALDSEVAASCGGAVLVGLMALTLSPHYKRYISWCLWW LQYFLTRVEALLHVWVPPLNVRGGRDAVILLMCVVHPALVFDITKLLLAVFGPLW ILQTSLLKVPYFVRVQGLLRICALVRKMAGGHYVQMAMIKVGALTGTYIYNHLTP LRDWAHNSLQDLAVAVEPVVFSQMETKLITWGADTAACGDIINNLPVSARRGQ EILLGPADGMASKGWRLLAPITAYAQQTRGLLGCIITSLTGRDKNQVEGEIQIVS TAAQTFLATCINGVCWSIYHGAGTRTIASPNGPVIQMYTNVDQDLVGWPAPQG ARSLTPCTCGSSDLYLVTRHADVIPVRRRGDGRGSLLSPRPISYLKGSSGGPLL CPAGHAVGLFRAAVCTRGVAKAVDFIPVEGLETTMRSPVFSDNSSPPAVPQCY QVAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGVD PNVRTGVRTITTGSPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSVLGIGT VLDQAETAGARLWLATATPPGSITVPHPNIEEVALSATGEIPFYGKAIPLEAIKG GRHLIFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVSTDALMT GFTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGRP GIYRFVAPGERPSGMFDSSVLCECYDAGCAVVYELTPAETTVRLRAYMNTPGLP VCQDHLEFWEGVFTGLTHIDAHFLSQTKQSGENLPYLVAYQATVCARAQAPPP SWDQMWKCLTRLKPTLHGPTPLLYRLGAVQNEITLTHPVTKYIMTCMSADLEVV TSTWVLVGGVLAALTAYCLSTGCVVIVGRIVLSGKPAVIPDREVLYREFDEMEE CSQHLPYIEHGMMLAEQFKQKALGLLQTASRQAEVIAPAVQTNWQKLEAFWAK HMWNFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTNQTLLFNILGGWLAA QLAAPGAATAFVGAGLTGAAIGSVGLGKVLVDILAGYGAGVAGALVAFKIMSGE TPSTEDLVNLLPAILSPGALVVGWCAAILRRHVGPGEGAVQWMNRLIAFASRG NHVSPTHYVPESDAAARVTAILGSLTVTQLLRRLHQWISSDCTTPCSGSWLRDV WDWICEVLSDFKTWLKAKLMPQLPGIPFVSCQRGYRGVWRGDGVMHTRCHC GAEITGHVRNGTMRIVGPRTCRNMWSGTFPINAYTTGPCSPLPAPNYKFALWR VSAEEYVEIRQVGDFHYVTGMTTDNLKCPCQIPSPEFFTELDGVRLHRYAPPCK PLLREEVSFRVGLHDYPVGSQLPCEPEPDVTVVTSMLTDPSHITAEAAARRLAR GSPPSMASSSASQLSAPSLKATCTTNHDSPDAELIEANLLWRQAMGGNITRVE SENKWILDSFDPLVAEEDEREISVPAEILRKSRRFAQALPVWARPDYNPPLIET WKKPDYEPPWHGCPLPPPQSPPVPPPRKKRTVVLTESTLSTALAELAAKSFG SSSTSGITGDDTTTSSEPASSGCPPDSDAESYSSMPPLEGEPGDPDLSDGSW STVSSGADAEDVVCCSMSYSWTGALITPCAAEEQKLPINALSNSLLRHHNLVYS TTSRSACLRQKKVTFDRLQVLDNHYQDVLKEVKAAASTVKANLLSVEEACSLTP PHSARSKFGYGAKDVRCHARKAVTHINSVWKDLLEDSVTPIDTTIMAKNEVFCV QPEKGGRKPARLIVFPDLSVRVCEKMALYDWSKLPQAVMGSSYGFQYSPGQ RVEFLVQAWKSKKTPMGFSYDTRCFDSTVTENDIRTEEAIYQCCDLDPQARVAI KSLTERLYVGGPLTNSKGENCGYRRCRASGVLTTSCGNTLTCYIKAKAACRAA GLRDCTMLVCGDDLVVICESQGVQEDAASLRAFTEAMTRYSAPPGDPPQPEY DLELITSCSSNVSVAHDSAGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNI IMFAPTLWARMILMTHFFSVLMARDQLEQALDCEIYGACYSIEPLDLPPIIQRLHG LSAFSLHSYSPGEINRVATCLRKLGVPPLRAWRHRARSVRAKLLSRGGRAAICG RYLFNWAVRTKLKLTPIAAAGQLDLSGWFTAGYSGGDIYHSVSRARPRWLWFC LLLLAAGVGIYLLPNR

Design21.mosaic1 Amino Acid Sequence SEQ ID NO: 22 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERSQPRGRRQPIPKARQPEGRAWAQPGYPWPLYGNEGMGWAGWLLSPRG SRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGV RVLEDGVNYATGNLPGCSFSIFLLALLSCLTIPASAYEVRNVSGVYHVTNDCSN SSIVYEAADMIMHTPGCVPCVRENNSSRCWVALTPTLAARNASVPTTTIRRHVD LLVGAAAFCSAMYVGDLCGSVFLVSQLFTFSPRRHETVQDCNCSIYPGHVSGH RMAWDMMMNWSPTTALWSQLLRIPQAVVDMVAGAHWGVLAGLAYYSMVGN WAKVLIVMLLFAGVDGHTHVTGGRVASSTQSLVSWLSQGPSQKIQLVNTNGS WHINRTALNCNDSLQTGFLAALFYTHKFNASGCPERMASCRPIDEFAQGWGPI THDMPESSDQRPYCWHYAPRPCGIVPASQVCGPVYCFTPSPVWGTTDRFGV PTYSWGENETDVLLLNNTRPPQGNWFGCTWMNSTGFTKTCGGPPCNIGGVG NNTLTCPTDCFRKHPEATYTKCGSGPWLTPRCLVDYPYRLWHYPCTVNFTIFK VRMYVGGVEHRLNAACNWTRGERCDLEDRDRSELSPLLLSTTEWQILPCSFTT LPALSTGLIHLHQNIVDVQYLYGIGSAWSFAIKWEYVLLLFLLLADARVCACLW MMLLIAQAEAALENLVVLNAASVAGAHGILSFLVFFCAAWYIKGRLVPGAAYALY GVWPLLLLLLALPPRAYAMDREMAASCGGAVFVGLALLTLSPHYKVFLARLIWW LQYFITRAEAHLQVWIPPLNVRGGRDAIILLTCAVHPELIFDITKLLLAILGPLMVLQ AGITRVPYFVRAQGLIRACMLVRKVAGGHYVQMAFMKLAALTGTYVYDHLTPL RDWAHAGLRDLAVAVEPWFSDMETKIITWGADTAACGDIILGLPVSARRGREIL LGPADSLEGQGWRLLAPITAYSQQTRGLLGCIITSLTGRDKNQVEGEVQVVSTA TQSFLATCVNGVCWTVYHGAGSKTLAGPKGPITQMYTNVDQDLVGWQAPPGA RSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPVSYLKGSSGGPLL CPSGHAVGIFRAAVCTRGVAKAVDFVPVESMETTMRSPVFTDNSSPPAVPQTF QVAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGVD PNIRTGVRTITTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSTDSTTILGIGTV LDQAETAGARLVVLATATPPGSVTVPHPNIEEVALSNTGEIPFYGKAIPIETIKGG RHLIFCHSKKKCDELAAKLSGLGLNAVAYYRGLDVSVIPTSGDVVVVATDALMT GFTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGR RGIYRFVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETSVRLRAYLNTPGL PVCQDHLEFWESVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARAQAPP PSWDQMWKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMACMSADLEV VTSTWVLVGGVLAALAAYCLTTGSVVIVGRIILSGKPAIIPDREVLYQEFDEMEEC ASHLPYIEQGMQLAEQFKQKALGLLQTATKQAEAAAPVVESKWRALETFWAKH MWNFISGIQYLAGLSTLPGNPAIASLMAFTASITSPLTTQHTLLFNILGGWVAAQL APPSAASAFVGAGIAGAAVGSIGLGKVLVDILAGYGAGVAGALVAFKVMSGEMP STEDLVNLLPAILSPGALWGWCAAILRRHVGPGEGAVQWMNRLIAFASRGNH VSPTHYVPESDAAARVTQILSSLTITQLLKRLHQWINEDCSTPCSGSWLRDVWD WICTVLTDFKTWLQSKLLPRLPGVPFFSCQRGYKGVWRGDGIMQTTCPCGAQI TGHVKNGSMRIVGPKTCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAAE EYVEVTRVGDFHYVTGMTTDNVKCPCQVPAPEFFTEVDGVRLHRYAPACKPLL REEVTFQVGLNQYLVGSQLPCEPEPDVAVLTSMLTDPSHITAETAKRRLARGSP PSLASSSASQLSAPSLKATCTTHHDSPDADLIEANLLWRQEMGGNITRVESENK WILDSFDPLRAEEDEREVSVPAEILRKSRKFPRAMPIWARPDYNPPLLESWKD PDYVPPWHGCPLPPTKAPPIPPPRRKRTWLTESTVSSALAELATKTFGSSES SAVDSGTATAPPDQPSDDGDAGSDVESYSSMPPLEGEPGDPDLSDGSWSTV SEEASEDVVCCSMSYTWTGALITPCAAEESKLPINALSNSLLRHHNMVYATTSR SASQRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSVEEACKLTPPHS ARSKFGYGAKDVRNLSSKAVNHIRSVWKDLLEDTETPIDTTIMAKNEVFCVQPE KGGRKPARLIVFPDLGVRVCEKMALYDWSTLPQAVMGSSYGFQYSPGQRVE FLVNAWKSKKCPMGFAYDTRCFDSTVTENDIRVEESIYQCCDLAPEARQAIRSL TERLYIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKASAACRAAKLQ DCTMLVCGDDLVVICESAGTQEDAASLRVFTEAMTRYSAPPGDPPQPEYDLELI TSCSSNVSVAHDASGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMYA PTLWARMILMTHFFSILLAQEQLEKALDCQIYGACYSIEPLDLPQIIQRLHGLSAF SLHSYSPGEINRVASCLRKLGVPPLRVWRHRARSVRAKLLSQGGRAATCGKYL FNWAVRTKLKLTPIPAASQLDLSGWFVAGYSGGDIYHSLSRARPRWFMWCLLL LSVGVGIYLLPNR

Design22.mosaic1 Amino Acid Sequence Seq ID NO: 23 MSTNPKPQRKIKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTS ERPQPRGRRQPIPKARQPEGRAWAQPGYPWPLYGNEGLGWAGWLLSPRGS RPSWGPTDPRRRSRNLGKVIDTLTCGLADLMGYIPLVGAPLGGVARALAHGVR VLEDGVNYATGNLPGCSFSIFLLALLSCLTIPASAYEVRNVSGVYHVTNDCSNAS IVYEAADMIMHTPGCVPCVRENNSSRCWVALTPTLAARNASVPTTTIRRHVDLL VGTAAFCSAMYVGDLCGSVFLVAQLFTFSPRRHETVQDCNCSIYPGHVTGHR MAWDMMMNWSPTAALVVSQLLRIPQAVMDMVAGAHWGILAGLAYYSMVGNW AKVLWMLLFAGVDGGTHVTGGKVAYTTQGFTSFFSRGPSQKIQLINTNGSWHI NRTALNCNDSLNTGFLAALFYTHKFNASGCPERMASCRSIDKFDQGWGPITYA EPHDLDQRPYCWHYAPRPCGIVPASEVCGPVYCFTPSPVWGTTDRFGVPTY SWGENETDVLLLNNTRPPQGNWFGCTWMNSTGFTKTCGAPPCNIGGVGNNT LTCPTDCFRKHPEATYARCGSGPWLTPRCLVDYPYRLWHYPCTVNFTIFKVRM YVGGVEHRLDAACNWTRGERCNLEDRDRSELSPLLLSTTEWQVLPCSFTTLPA LSTGLIHLHQNIVDVQYLYGVGSAVVSFVIKWEYVLLLFLLLADARICACLWMML LIAQAEAALENLVVLNAASVAGTHGILPFLVFFCAAVVYIKGRLVPGAAYALYGVW PLLLLLLALPPRAYAMDREVAASCGGAVFIGLALLTLSPHYKVFLAKLIWWLQYFI TRTEAHLQVWIPPLNVRGGRDAIILLTCAIHPELIFTITKILLAILGPLMVLQAGITKV PYFVRAHGLIRACMLVRKVAGGHYVQMALMKLAALTGTYVYDHLTPLRDWAHA GLRDLAVAVEPVVFSDMETKVITWGADTAACGDIILGLPVSARRGREILLGPADS LEGQGWRLLAPITAYAQQTRGLLGCIITSLTGRDKNQVEGEVQVVSTATQSFLA TCINGVCWTVFHGAGSKTLAGPKGPVTQMYTNVDQDLVGWQAPPGARSLTPC TCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPVSYLKGSSGGPLLCPSGHA VGIFRAAVCTRGVAKAVDFVPVESMETTMRSPVFTDNSSPPAVPQSFQVAHLH APTGSGKSTRVPAAYAAQGYKVLVLNPSVAATLSFGAYMSKAHGVDPNIRTGV RTITTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSTDSTSILGIGTVLDQAETA GARLWLATATPPGSVTVPHPNIEEVALSNIGEIPFYGKAIPIETIKGGRHLIFCHS KKKCDELAAKLSGLGLNAVAYYRGLDVSVIPTSGDWWATDALMTGYTGDFD SVIDCNTCVIQTVDFSLDPTFTIETTTVPQDAVSRTQRRGRTGRGRGGIYRFVTP GERPSGMFDSSVLCECYDAGCAWYELTPAETSVRLRAYLNTPGLPVCQDHLE FWESVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARSQAPPPSWDQMW KCLTRLKPTLHGPTPLLYRLGAVQNEVILTHPITKYIMACMSADLEIVTSTWVLVG GVLAALAAYCLTTGCVVIVGRIILSGKPAIIPDREVLYREFDEMEECASHLPYIEQ GMQLAEQFKQKAIGLLQTATKQAEAAVPVVESKWRALEAFWAKHMWNFISGIQ YLAGLSTLPGNPAIVSLMAFTASITSPLTTQHTLLFNILGGWVAAQLAPPRAASA FVGAGIVGAAVGSVGLGKVLVDVLAGYGAGVAGALVAFKIMSGEVPSTEDLVNL LPAILSPGALWGVVCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVP ESDAAARVTQILSSLTITQLLRRLHQWINEDCSTPCSGSWLRDVWDWICTVLTD FKTWLQSKLMPRLPGVPFLSCQRGYRGVWRGDGIMHTTCPCGAQITGHVKNG SMRIVGPKTCSNTWHGTFPINAHTTGPCTPSPAPNYSRALWRVAAEEYVEVTR VGDFHYVTGMTTDNIKCPCQVPAPEFFTELDGVRLHRYAPACKPLLRDEVTFQ VGLNQYPVGSQLPCEPEPDVTVLTSMLTDPSHITAETAKRRLARGSPPSLARSS ASQLSAPSLKATCTTHHDSPDADLIEANLLWRQEMGGNITRVESENKVVILDSF DPLRAEEDEREVSVAAEILRKSRKFPPALPIWARPDYNPPLIESWKDPDYVPPL VHGCPLPPTKAPPIPPPRRKRTVVLTESTVSSALAELATKTFGSSESSAVDSGT ATAPPDQPSDDGDAGSDVESYSSMPPLEGEPGDPDLNDGSWSTVSEEASED WCCSMSYSWTGALITPCAAEESKLPINALSNSLLRHHNMVYATTSRSASQRQ KKVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSVEEACKLTPPHSARSKFG YGAKDVRNLSSKAVNHIHSVWKDLLEDTETPIDTTIMAKSEVFCVQPEKGGRKP ARLIVYPDLGVRVCEKMALYDVVSTLPQAVMGSSYGFQYSPGQRVEFLVNAW KSKKCPMGFAYDTRCFDSTVTENDIRVEESIYQCCDLAPEARQAIKSLTERLYIG GPLTNSKGQSCGYRRCRASGVLTTSCGNTLTCYLKASAACRAAKLQDCTMLV CGDDLWICDSAGTQEDAASLRVFTEAMTRYSAPPGDPPKPEYDLELITSCSSN VSVAHDASGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMYAPTLWAR MILMTHFFSILLAQEQLEKALDCQIYGATYSIEPLDLPQIIQRLHGLSAFTLHSYSP GEINRVAACLRKLGVPPLRVWRHRARSVRARLLSQGGRAATCGKYLFNWAVR TKLKLTPIPAASRLDLSGWFVAGYSGGDIYHSLSRARPRWFMWCLLLLSVGVGI YLLPNR

Design22.mosaic2 Amino Acid Sequence SEQ ID NO: 24 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPKLGVRATRKT SERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGMGWAGWLLSPRG SRPSWGPNDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGV RVLEDSVNYATGNLPGCSFSIFLLALLSCLTVPASAYEVRNASGVYHVTNDCSN SSIVYEAADVIMHTPGCVPCVREGNSSRCWVALTPTLAARNSSIPTTTIRRHVDL LVGAAAFCSAMYVGDLCGSVFLVSQLFTFSPRRYETVQDCNCSIYPGHVSGHR MAWDMMMNWSPTTALVVSQLLRIPQAVVDMVAGAHWGVLAGLAYYSMAGN WAKVLIVMLLFAGVDGHTHVTGGRVASSTQSLVSWLSQGPSQKIQLVNTNGS WHINRTALNCNDSLQTGFLAALFYTHRFNSSGCPERMASCRPIDKFAQGWGPI THVVPNISDQRPYCWHYAPQPCGIVPASQVCGPVYCFTPSPVVVGTTDRSGVP TYNWGENETDVLILNNTRPPRGNWFGCTWMNGTGFTKTCGGPPCNIGGAGN NTLICPTDCFRKHPEATYTKCGSGPWLTPRCMVDYPYRLWHYPCTVNFTVFKV RMYVGGVEHRLNAACNWTRGERCDLEDRDRSELSPLLLSTTEWQILPCSFTTL PALSTGLIHLHRNIVDVQYLYGIGSAVVSFAIKWEYVVLLFLLLADARVCACLWM MLLVAQAEAALENLVVLNAASVAGAFIGILSFLVFFCAAVVYIKGKLVPGAAYAFY GVWPLLLLLMALPARAYAMDREMAASCGGAVFVGLVLLTLSPYYKVFLARLIW WLQYFITRAEAHLQVWVPPLNVRGGRDAIILLTCAVHPELIFDITKLLLAILGPLMV LQAGITRVPYFVRAQGLIRACMLVRKAAGGHYVQMAFMKLAALTGTYVYNHLT PLQDWAHAGLRDLAVAVEPVIFSDMETKIITWGADTAACGDIISGLPVSARRGK EILLGPADSFGEQGWRLLAPITAYSQQTRGLLGCIVTSLTGRDRNQVEGEVQM VSTATQSFLATCVNGVCWTVYHGAGSKTLAGPKGPITQMYTNVDQDLVGWPA PPGARSMTPCTCGSSDLYLVTRHADVIPVRRRGDGRGSLLSPRPISYLKGSSG GPLLCPSGHWGIFRAAVCTRGVAKAVDFIPVESMETTMRSPVYTDNSSPPAVP QTFQVAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHG IDPNIRTGVRTITTGASITYSTYGKFLADGGCSGGAYDIIMCDECHSTDSTTILGIG TVLDQAETAGVRLTVLATATPPGSVTVPHSNIEEVALSNTGEIPFYGKAIPIEAIK GGRHLIFCHSRKKCDELAAKLSALGVNAVAYYRGLDVSVIPASGDWWATDAL MTGFTGDFDSVIDCNTCVTQTVDFSLDPTFTIDTTTVPQDAVSRSQRRGRTGR GRRGIYRFVTPGERPSGMFDSWLCECYDAGCAWYELTPAETTVRLRAYLNTP GLPVCQDHLEFWEGVFTGLTHIDAHFLSQTKQAGENFPYLTAYQATVCARAQA PPPSWDQMWKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKFIMACMSADL EVVTSTWVLVGGVLAALAAYCLTTGSVVIVGRIILSGRPAVIPDREVLYQEFDEM EECATHLPYIEQGMQLAEQFKQKALGLLQTATKQAEAAAPWESKWRALETFW AKHMWNFISGVQYLAGLSTLPGNPAIASLMAFTASVTSPLTTQSTLLFNILGGW VAAQLAPPSAASAFVGAGIAGAAVGSIGLGKVLVDILAGYGAGVAGALVAFKVM SGEMPSTEDLVNLLPAILSPGALWGVVCAAVLRRHVGPGEGAVQWMNRLIAF ASRGNHVSPTHYVPESDAAVRVTQILSSLTITQLLKRLHQWINEDCSTPCSGSW LKDVWDWICTVLSDFKTWLQSKLLPRLPGVPFFSCQRGYKGVWRGDGIMQTT CPCGAQIAGHVKNGSMRIVGPRTCSNTWHGTFPINAYTTGPCTPSPAPNYSKA LWRVAAEEYVEVTRVGDFHYVTGMTTDNVKCPCQVPAPEFFTEVDGVRLHRY APACKPLLREEVTFQVGLNQYLVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAK RRLARGSPPSLASSSASQLSAPSLKATCTTRHDSPDADLIEANLLWRQEMGGNI TRVESENKVWLDSFEPLRAEEDEREVSVPAEILRKSRKFPRAMPIWARPDYNP PLLESWKDPDYVPPWHGCPLPPAKAPPIPPPRRKKTWLTESTVSSALAELAT KTFGSSGSSAVDSGTATAPPDQASDDGDKGSDVESYSSMPPLEGEPGDPDLS DGSWSTVSEEAGEDVVCCSMSYTWTGALITPCAAEESKLPINPLSNSLLRHHS MVYSTTSRSASLRQKKVTFDRLQVLDDHYQDVLKEMKAKASTVKAKLLSIEEAC KLTPPHSAKSKFGYGAKDVRSLSSKAVNHIRSVWKDLLEDTVTPIDTTIMAKNEV FCVQPEKGGRKPARLIVFPDLGVRVCEKMALYDWSTLPQAVMGPSYGFQYSP KQRVEFLVNTWKSKKCPMGFSYDTRCFDSTVTESDIRVEESIYQCCDLAPEAR QAIRSLTERLYVGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKATAAC RAAKLQDCTMLVNGDDLVVICESAGTQEDAANLRVFTEAMTRYSAPPGDPPQP EYDLELITSCSSNVSVAHDATGKRVYYLTRDPTTPLARAAWETVRHTPVNSWL GNIIMYAPTLWARMVLMTHFFSILIAQEQLEKALDCQIYGACYSIEPLDLPQIIERL HGLSAFSLHSYSPGEINRVASCLRKLGVPPLRAWRHRARSVRAKLLSQGGRAA VCGKYLFNWAVKTKLKLTPIPAASQLDLSGWFVAGYSGGDIYHSVSRARPRWF MLCLLLLSVGVGIYLLPNR

Design23.mosaic1 Amino Acid Sequence SED ID NO: 25 MSTNPKPQRQTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPKLGVRATRKT SERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGMGWAGWLLSPRG SRPSWGPNDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGVARALAHGV RVVEDGVNYATGNLPGCSFSIFLLALLSCLTTPASAYEVRNVSGIYHVTNDCSN SSIVYEAADVIMHTPGCVPCVREDNSSRCWVALTPTLAARNSSIPTTTIRRHVDL LVGAAALCSAMYVGDFCGSVFLVSQLFTFSPRQHETVQDCNCSIYPGHVSGHR MAWDMMMNWSPTTALVVSQLLRIPQAIVDMVAGAHWGVLAGLAYYSMAGNW AKVLIVMLLFAGVDGHTHVTGGRVASSTQSLVSWLSQGPSQKIQLVNTNGSWH INRTALNCNDSLQTGFLAALFYTHKFNASGCPERMASCRPIDKFAQGWGPITYA GSCGLDQRPYCWHYAPQPCGIVPAAQVCGPVYCFTPSPWVGTTDRFGAPTY NWGENETDVLILNNTRPPQGNWFGCTWMNSTGFTKTCGAPPCNIGGVGNNTL TCPTDCFRKHPDATYTKCGSGPWLTPRCMVDYPYRLWHYPCTVNFTVFKVRM YVGGVEHRLNAACNWTRGERCDLEDRDRSELSPLLLSTTEWQILPCAFTTLPA LSTGLIHLHRNIVDVQYLYGVGSAVVSFAIKWEYILLLFLLLADARVCACLWMML LIAQAEATLENLVVLNAASVAGTHGILPFLVFFCAAVVYIKGRLVPGAAYALYGVW PLLLLLLALPPRAYAMDREVAASCGGAVFVGLVLLTLSPYYKVFLARLIWWLQYF ITRAEAHLQVWVPPLNVRGGRDAIILLMCVVHPELIFDITKLLLAILGPLMVLQAGI TRVPYFVRAQGLIRACMLVRKVVGGHYVQMAFMKLAALTGTYVYDHLTPLQD WAHAGLRDLAAAVEPVVFSDMETKIITWGAETAACGDIISGLPVSARRGKEILLG PADSFGEQGWRLLAPITAYSQQTRGLLGCIITSLTGRDKNQVDGEVQVLSTATQ SFLATCINGVCWTVYHGAGSKTLAGPKGPITQMYTNVDQDLVGWPAPPGARS MTPCTCGSSDLYLVTRHADVIPVRRRGDNRGSLLSPRPVSYLKGSSGGPLLCP SGHVVGIFRAAVCTRGVAKAVDFVPVESMETTMRSPVFTDNSSPPAVPQTFQV SHLHAPTGSGKSTKVPAAYASQGYKVLVLNPSVAATLGFGAYMSKAYGVDPNI RTGVRTITTGASITYSTYGKFLADGGCSGGAYDIIICDECHSTDATTILGVGTVLD QAETAGARLVVLATATPPGSVTVPHSNIEEVALSNTGEIPFYGKAIPIEAIKGGRH LIFCHSKKKCDELATKLSALGINAVAYYRGLDVSVIPTSGDVVVVATDALMTGFT GDFDSVIDCNTCWQTVDFSLDPTFTIETTTVPQDAVSRTQRRGRTGRGRRGIY RFVTPGERPSGMFDSVVLCECYDAGCAWYELTPAETTVRLRAYLNTPGLPVC QDHLEFWEGVFTGLTHIDAHFLSQTKQAGDNFPYLTAYQATVCARAQAPPPSW DQMWKCLTRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMTCMSADLEWTS TWVLVGGVLAALAAYCLTTGCWIVGRIILSGKPAVIPDREALYQEFDEMEECAT HLPYIEQGMQLAEQFKQKALGLLQTASKQAEAAAPVVESKWRALEAFWAKHM WNFISGVQYLAGLSTLPGNPAIASLMAFTASVTSPLTTQSTLLFNILGGWVAAQL APPSAASAFVGAGIAGAAIGSIGLGKVLVDILAGYGAGVAGALVAFKVMSGDMP STEDLVNLLPAILSPGALWGWCAAILRRHVGPGEGAVQWMNRLIAFASRGNH VSPTHYVPESDAAARVTQILSSLTITQLLRRLHQWINEDCSTPCSGSWLKDVWD WICTVLADFKTWLQSKLLPRLPGLPFLSCQRGYKGVWRGDGVMQTTCPCGAQ ISGHVKNGSMRIVGPRTCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAA EEYVEITRVGDFHYVTGMTTDNVKCPCQVPAPEFFTEVDGVRLHRYAPACRPL LREEWFQVGLNQYPVGSQLPCEPEPDVTWTSMLTDPSHITAEAAKRRLARG SPPSLASSSASQLSALSLKATCTTRHDSPDVDLIEANLLWRQEMGGNITRVESE NKVVILDSFEPLQAEEDEREVSVAAEILRKSRKFPPAMPVWARPDYNPPLLESW KDPDYVPPWHGCPLPPTKAPPIPPPRRKKTWLTESTVSSALAELATKTFGSS GSSAVDSGTATAPPDQASDDGDKGSDVESYSSMPPLEGEPGDPDLSDGSWS TVSGEAGEDVVCCSMSYTWTGALITPCAAEESKLPINPLSNSLLRHHSMVYSTT SRSASLRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSIEEACKLTPPH SAKSKFGYGAKDVRNLSSRAVNHIRSVWEDLLEDTETPIDTTIMAKSEVFCVQP EKGGRKPARLIVYPDLGVRVCEKMALYDWSTLPQAVMGPSYGFQYSPGQRV EFLVNAWKSKKCPMGFAYDTRCFDSTVTENDIRTEESIYQCCDLDPEARQAIRS LTERLYVGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKATAACRAAKL QDCTMLVNGDDLVVICESAGTQEDAANLRVFTEAMTRYSAPPGDLPQPEYDLE LITSCSSNVSVAHDAAGKRVYYLTRDPTTPLARAAWETVRHTPVNSWLGNIIMY APTLWARMVLMTHFFSILIAQEQLEKALDCQIYGACYSIEPLDLPQIIERLHGLSA FSLHSYSPGEINRVASCLRKLGVPPLRTWRHRARSVRAKLLSQGGRAAICGRY LFNWAVRTKLKLTPIPAASRLDLSGWFVAGYGGGDIYHSLSRARPRWFMLCLLL LSVGVGIYLLPNR

Design23.mosaic2 Amino Acid Sequence SEQ ID NO: 26 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRAPRKT SERSQPRGRRQPIPKARRPEGRAWAQPGYPWPLYGNEGLGWAGWLLSPRG SRPSWGPSDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGV RVLEDSVNYATGNLPGCSFSIFLLALLSCLTIPASAYEVRNASGVYHVTNDCSNA SIVYEAADMIMHTPGCVPCVRENNSSRCWVALTPTLAARNASVPTTTIRRHVDL LVGTAAFCSAMYVGDLCGSVFLVSQLFTFSPRRHETVQDCNCSIYPGHVTGHR MAWDMIMNWSPTTALVVSQLLRIPQAVVDMVAGAHWGILAGLAYYSMVGNWA KVLVVMLLFAGVDGGTHVTGGKVAYTTQGFTSFFSRGPSQKIQLVNTNGSWHI NRTALNCNDSLNTGFLAALFYTHRFNSSGCPERMASCRSIDKFDQGWGPITYA EPGSSDQRPYCWHYAPKPCGIVPASQVCGPVYCFTPSPWVGTTDRFGVPTY SWGENETDVLLLNNTRPPQGNWFGCTWMNGTGFTKTCGGPPCNIGGAGNNT LICPTDCFRKHPEATYTKCGSGPWLTPRCLVDYPYRLWHYPCTVNFTIFKVRM YVGGVEHRLEAACNWTRGERCNLEDRDRSELSPLLLSTTEWQILPCSFTTLPA LSTGLIHLHQNWDVQYLYGIGSAWSFAIKWEYVLLLFLLLADARICACLWMML LIAQAEAALENLVVINAASVAGAHGFLSFLVFFCAAWYIKGRLVPGAAYAIYGVW PLFLLLLALPPRAYAMDREMAASCGGAVFVGLALLTLSPHYKVFLAKLIWWLQY LITRAEALLQVWVPPLNVRGGRDAIILLTCAIHPELIFTITKILLAILGPLMVLQAGIT KVPYFVRAHGLIRACMLVRKVAGGHYVQMALMKLAALTGTYVYDHLTPLRDWA HAGLRDLAVAVEPVVFSDMETKVITWGADTAACGDIILGLPVSARRGKEIFLGPA DSLEGQGWRLLAPITAYAQQTRGLLGCIVTSLTGRDRNQVEGEVQVVSTATQS FLATCVNGVCWTVYHGAGTKTLAGPKGPIIQMYTNVDQDLVGWQAPPGARSL TPCTCGSSDLYLVTRHADVIPVRRRGDGRGSLLSPRPISYLKGSSGGPLLCPLG HVVGIFRAAVCTRGVAKAVDFIPVESLETTMRSPVYTDNSSPPAVPQSFQVAHL HAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTG VRTITTGAPVTYSTYGKFLADGGCSGGAYDIIMCDECHSTDSTTILGIGTVLDQA ETAGARLVVLATATPPGSVTVPHPNIEEVALSNIGEIPFYGKAIPIETIKGGRHLIF CHSRKKCDELAAKLSGLGLNAVAYYRGLDVSVIPASGDWWATDALMTGFTG DFDSVIDCNTCVIQTVDFSLDPTFTIDTTTVPQDAVSRSQRRGRTGRGRMGIYR FVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETSVRLRAYLNTPGLPVCQ DHLEFWESVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARSQAPPPSWD QMWKCLIRLKPTLHGSTPLLYRLGAVQNEVILTHPITKYIMACMSADLEVATSTW VLVGGVLAALAAYCLTAGSVVIVGRIILSGKPAIIPDREVLYREFDEMEECASQLP YIEQGMQLAEQFKQKAIGLLQTATKQAEAAVPWESKWRTLEAFWAKHMWNFI SGIQYLAGLSTLPGNPAIVSLMAFTASITSPLTTQHTLLFNILGGWVAAQLAPPRA ASAFVGAGIAGAAVGSIGLGKVLVDVLAGYGAGVAGALVAFKVMSGEMPSTED LVNLLPAILSPGALVVGWCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVSPT HYVPESDAAVRVTQILSSLTITQLLKRLHRWINEDCSTPCAGSWLRDVWDWICT VLTDFKTWLQSKLLPRLPGVPFFSCQRGYKGVWRGDGIMHTTCPCGAQIAGH VKNGSMKIVGPKTCSNTWHGTFPINAHTTGPCTPSPAPNYSKALWRVAAEEYV EVTRVGDFHYVTGMTTDNLKCPCQVPAPEFFTELDGVRLHRYAPACKPLLREE VTFQVGLNQYLVGSQLPCEPEPDVAVLTSMLTDPSHITAETARRRLARGSPPSL ASSSASQLSAPSLKATCTTRHDSPDADLIEANLLWRQEMGGNITRVESENKVW LDSFEPLRAEEDEREVSVPAEILRKSRKFPRAMPIWARPDYNPPLIESWKDPDY APPWHGCPLPPTKTPPIPPPRRKRTWLTESTVSSALAELATKTFGSSESSAAD SGTATAPPDQPSDDGDAGSDVESYSSMPPLEGEPGDPDLSDGSWSTVSEEA GEDVVCCSMSYSWTGALITPCAAEETKLPINALSNSLLRHHNLVYATTSRSAGL RQKKVTFDRLQVPDDHYRDVLKDMKAKASTVKAKLLSVEEACRLTPPHSARSK FGYGAKDVRSLSSKAVNHIRSVWKDLLEDTDTPIDTTIMAKNEVFCIQPEKGGR KPARFIVFPDLGVRVCEKMALYDVVSTLPQAVMGSSYGFQYSPKQRVEFLVNT WKSKKCPMGFSYDTRCFDSTVTESDIRVEESIYQCCDLAPEARQAIRSLTERLYI GGPLTNSKGQSCGYRRCRASGVLTTSCGNTLTCYLKAAAACRAAKLRDCTML VCGDDLVVICESAGTQEDEASLRAFTEAMTRYSAPPGDPPKPEYDLELITSCSS NVSVAHDASGKRVYYLTRDPATPLARAAWETARSTPVNSWLGNIIMYAPTLWA RMILMTHFFSILLVQEQLEKALDCQIYGAYYSIEPLDLPQIIERLHGLSAFSLHSYS PGEINRVAACLRKLGVPPLRVWRHRARSVRARLLSQGGRAATCGKYLFNWAV RTKLKLTPIPAASQLDLSSWFVAGYSGGDIYHSLSRARPRWFMFCLLLLSVGVG VYLLPNR

Design23.mosaic3 Amino Acid Sequence SEQ ID NO: 27 MSTNPKPQRKIKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTS ERPQPRGRRQPIPKARQPEGRAWAQPGYPWPLYGNEGCGWAGWLLSPRGS RPSWGPTDPRRRSRNLGKVIDTLTCGLADLMGYIPLVGGPLGGAARALAHGVR VLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAYEVRNVSGVYHVTNDCSNS SIVYETADMIMHTPGCVPCVREGNSSRCWVALTPTLAARNASVPTTAIRRHVDL LVGAAAFCSAMYVGDLCGSVFLISQLFTFSPRRYETVQDCNCSLYPGHITGHR MAWDMMMNWSPTAALVVSQLLRIPQAVVDIVAGAHWGILAGLAYYSMVGNWA KVLIVLLLFAGVDGNTRVSGGEAAKNTMGFASLFVSGPSQKIQLINTNGSWHIN RTALNCDDSLHTGFLAALFYAHKFNSSGCSGRMASCRPIDEFAQGWGPITHGV PDNLDQRPYCWHYAPRPCGIVPASEVCGPVYCFTPSPVWGTTDRSGVPTYT WGENETDVLLLNNTRPPRGNWFGCTWMNGTGFTKTCGGPPCNIGGVGNDTLI CPTDCFRKHPEATYAKCGSGPWLTPRCIVDYPYRLWHYPCTVNFSIFKVRMYV GGVEHRLDAACNWTRGERCDLEDRDRTELSPLLLSTTEWQVLPCSFTTLPALS TGLIHLHQNIVDVQYLYGIGSVVVSFAIKWEYVVLLFLLLADARFCACLWMMLLV AQAEAALENLVVLNAASVAGAHGILSFLVFFCAAVVYIKGKLVPGAAYAFYGVWP LLLLLMALPPRAYALDREMAASCGGAVFIGLALLTLSPHYKAFLARLIWWLQYLIT RAEAHLQVWIPPLNVRGGRDAIILLTCAVHPELIFEITKILLAIFGPLMVLQAGLTR VPYFVRAQGLIRACMLVRKAAGGHYVQMALMRLAALTGTYVYNHLTPLRDWA HTGLRDLAVAVEPVIFSDMETKIITWGADTAACGDILSGLPVSARRGREILLGPA DSFEGQGWRLLAPITAYSQQTRGLFGCIITSLTGRDKNQVEGEVQVVSTATQSF LATCVNGVCWTVFHGAGSKTLAGPKGPVTQMYTNVDQDLVGWQAPSGARSL TPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPLLCPSG HAVGIFRAAVCTRGVAKAVDFIPVESMETTMRSPVFTDNSTPPAVPQTFQVAHL HAPTGSGKSTRVPAAYAAQGYKVLVLNPSVAATLSFGAYMSKAHGVDPNIRTGI RTITTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSTDSTSILGIGTVLDQAETA GARLVVLATATPPGSITVPHPNIEEVALPNTGEIPFYGKAIPIEVIKGGRHLIFCHS KKKCDELAAKLSALGVNAVAYYRGLDVSVIPTSGNWWATDALMTGYTGDFD SVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRSQRRGRTGRGRGGIYRFVT PGERPSGMFDSSVLCECYDAGCAVVYELTPAVTSVRLRAYLNTPGLPVCQVHL EFWESVFTGLTHIDAHFLSQTKQAGENFPYLVAYQATVCARAKAPPPSWDQM WKCLIRLKPTLHGPTPLLYRLGAVQNEITLTHPITKFIMACMSADLEWTSTWVL VGGVLAALAAYCLTTGSVVIVGRIILSGRPAVIPDREVLYQEFDEMEECASHLPYI EQGVQLAEQFKQKALGLLQTATKQAEAAAPMVESKWRALETFWAKHMWNFIS GIQYLAGLSTLPGNPPIASLMAFTASITSPLTTQNTLLFNILGGWVAAQLAPPSAA SAFVGAGIVGAAVGSVGLGKVLVDILAGYGAGVAGALVAFKIMSGEVPSTEDLV NLLPAILSPGALVVGVVCAAVLRRHVGPGEGAVQWMNRLIAFASRGNHVSPTH YVPESDAAARVTQILSNLTITQLLKRLHQWINEDCSTPCSGSWLRDVWDWICTV LSDFKTWLQSKLLPRLPGVPFLSCQRGYRGVWRGDGIMQTTCPCGAQITGHV KNGSMRIVGPKTCSNTWRGSFPINAYTTGPSTPSPAPNYTFALWRVSAEEYVE VRRLGDFHYVTGMTTDNIKCPCQVPAPEFFTELDGVRLHRYAPACKPLLRDEV TFQVGLNQYVVGSQLPCEPEPDVTVLTSMLTDPSHITAETAKRRLARGSPPSLA RSSASQLSAPSLKATCTTHHDSPDADLIEANLLWRQEMGGNITRVESENKVVIL DSFDPLRAEEDEREISVPAEILRKTRKFPPALPIWARPDYNPPLLESWRDPDYV PPWHGCPLPPAKAPPVPPPRRKRTWLSESTVSSALAELATKTFGSSESSAVD SGTATAPPDQPSDNGDTGSDVESYSSMPPLEGEPGDPDFSDGSWSTVSEEAS EDVVCCSMSYTWTGAMITPCAAEESKLPINALSNSLLRHHNMVYATTSRSASQ RQKKVTFDRLQVLDNHYQDVLKEMKAKASTVKARLLSVEEACKLTPPHSARSK FGYGAKDVRNLSSKAVNHIHSVWKDLLEDTETPIDTTVMAKNEVFCVQPEKGG RKPARLIVFPDLGVRVCEKMALYDWSNLPQAVMGSAYGFQYSPGQRVEFLVN AWKSKKNPMGFAYDTRCFDSTVTENDIRVEESIYQSCDLAPEARQAIKSLTERL YIGGPLTNSKGQNCGYRRCRVSGVLTTSCGNTLTCYLKASAACRAAKLQDCTM LVCGDDLVVICDSAGTQEDAASLRVFTEAMTRYSAPPGDPPQPEYDLELITSCS SNVSVAHDATGKRVYYLTRDPTTPIARAAWETARHTPVNSWLGNIIMYAPTLWV RMILMTHFFSILLAQEQLEKALDCQIYGATYSIEPLDLPQIIQRLHGLSAFSLHSYS PGEINRVASCLRKLGVPPLRAWRHRARSVRAKLLSRGGRAATCGRYLFNWAV KTKLKLTPIPAASQLDLSGWFVAGYSGGDIYHSVSRARPRWFMWCLLLLSVGV GIYLLPNR

Design24.mosaic1 Amino Acid Sequence SEQ ID NO: 28 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERPQPRGRRQPIPKARQPEGRAWAQPGYPWPLYGNEGLGWAGWLLSPRG SRPSWGPNDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGV RVLEDSVNYATGNLPGCSFSIFLLALLSCLTVPASAYEVRNVSGVYHVTNDCSN SSIVYEAADIIMHTPGCVPCVRENNSSRCWVALTPTLAARNASVPTTTIRRHVDL LVGAAAFCSAMYVGDLCGSIFLVGQLFTLSPRRHWTTQDCNCSIYPGHVTGHR MAWDMMMNWSPTTALVLSQLLRIPQAVVDMVAGAHWGILAGLAYYSMAGNW AKVLIVMLLFAGVDGGTHVTGGKVAYTTQGFTSFFSRGPSQKIQLVNTNGSWHI NRTALNCNDSLNTGFLAALFYTHRFNSSGCPERMASCSPIDAFAQGWGPITYN ESHSSDQRPYCWHYPPQPCGIVPAAQVCGPVYCFTPSPVWGTTDRFGVPTY TWGENETDVLLLNNTRPPRGNWFGCTWMNSTGFTKTCGGPPCKIGGVGNNT LTCPTDCFRKHPEATYTRCGSGPWLTPRCLVHYPYRLWHYPCTVNFTIFKVRM YVGGVEHRLEAACNWTRGERCNLEDRDRSELSPLLLSTTEWQILPCSYTTLPA LSTGLIHLHQNTVDVQYLYGIGSVVVSFAIKWEYVLLLFLLLADARVCACLWMML LIAQAEAALENLVVLNAASLAGAHGILSFLVFFCAAVVYIKGRLVPGAAYAFYGVW PLFLLLLALPPRAYALDREMAASCGGAVFVGLALLTLSPHYKLFLARLIWWLQYF ITRAEAHLQVWIPPLNVRGGRDAIILLTCAIHPELIFTITKILLAILGPLMVLQAGITK VPYFVRAHGLIRACMLVRKVAGGHYVQMALMKLAALTGTYVYDHLTPLRDWAH TGLRDLAVAVEPVIFSDMETKVITWGADTAACGDIILGLPVSARRGKEIFLGPAD SLEGQGWRLLAPITAYAQQTRGLLGCIITSLTGRDRNQVEGEVQWSTATQSFL ATCVNGVCWTVFHGAGSKTLAGAKGPITQMYTNVDQDLVGWQAPSGARSLTP CTCGSSDLYLVTRHADVIPVRRRGDGRGSLLSPRPVSYLKGSSGGPLLCPLGH AVGIFRAAVCTRGVAKAVDFIPVESMETTMRSPVYTDNSSPPAVPQSFQVAHL HAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTG VRTITTGGPITYSTYGKFLADGGCSGGAYDIIICDECHSTDSTTILGIGTVLDQAE TAGARLVVLATATPPGSITVPHPNIEEVALSNIGEIPFYGKAIPIETIKGGRHLIFCH SKKKCDELAAKLSGLGLNAVAYYRGLDVSVIPTSGDVVVVATDALMTGYTGNF DSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRSQRRGRTGRGRMGIYRFV TPGERPSGMFDSWLCECYDAGCAWYELTPAETSVRLRAYLNTPGLPVCQDH LEFWEGVFTGLTHIDAHFLSQTKQAGDNLPYLVAYQATVCARAQAPPPSWDQ MWKCLTRLKPTLHGPTPLLYRLGAVQNEVTLTHPVTKYIMACMSADLEWTST WVLVGGVLAALAAYCLTTGCVVIVGRIILSGKPAIIPDREVLYQEFDEMEECASH LPYIEHGMHLAEQFKQKAIGLLQTATKQAEAAAPVVESKWRTLEAFWAKHMWN FISGIQYLAGLSTLPGNPAIVSLMAFTASITSPLTTQHTLLFNILGGWVAAQLAPP SAASAFVGAGIAGAAIGSIGLGKVLVDILAGYGAGVAGALVAFKIMSGEAPSTED LVNLLPAILSPGALVVGIVCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVSPT HYVPESDAAARVTQILSSLTITQLLKRLHQWISEDCSTPCSGSWLRDIWDWICT VLTDFRTWLQSKLLPRLPGVPFLSCQRGYRGVWRGDGIMHTTCPCGAQISGH VKNGSMRIVGPRTCSNTWHGTFPINAHTTGPCTPSPAPNYSTALWRVAAEEYV EVRRVGDFHYVTGMTTDNIKCPCQVPAPEFFTEVDGIRLHRYAPACKPLLREEV TFQVGLNQYLVGSQLPCEPEPDVSVLTSMLTDPSHITAETARRRLARGSPPSLA SSSASQLSAPSLRATCTTHSSYNLDSPDVDLIEANLLWRQEMGGNITRVESENK IVILDSFDPLRAEEDEREVSVPAEILRRSRKFPPAMPIWARPDYNPPLLEPWKDP DYVPPVVHGCPLPPAKAPPIPPPRRKRTWLSESTVSSALAELATKTFSSSESS AVDSGTATAPPDQPSDDGDAGSDVESYSSMPPLEGEPGDPDLSDGSWSTVS EEASEDWCCSMSYTWTGALITPCAAEETKLPINALSNSLLRHHNLVYATTSRS ASQRQRKVTFDRLQVPDDHYRDVLKEMKAKASTVKAKLLSIEEACKLTPPHSAK SKYGYGAKDVRSLSSKAVNHIRSVWKDLLEDTETPIDTTVMAKNEVFCVQPEK GGRKAARLIVFPDLGVRVCEKMALYDVVSTLPQAVMGSAYGFQYSPGQRVEFL VNAWKSKKSPMGFAYDTRCFDSTVTESDIRTEESIYQCCDLAPEARQVIRSLTE RLYIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKAAAACRAAKLQDC TMLVCGDDLVVICESAGTQEDEASLRAFTEAMTRYSAPPGDPPKPEYDLELITS CSSNVSVAHDATGKRVYYLTRDPTIPLARAAWETAKHTPVNSWLGNIIMYAPTL WVRMILMTHFFSILLVQEQLEKALDCQIYGAYYSIEPLDLPQIIERLHGLSAFSLH SYSPGEINRVASCLRKLGVPPLRTWRHRARSVRAKLLSQGGRAAICGRYLFNW AVRTKLKLTPISAASQLDLSSWFVAGYSGGDIYHSLSRARPRWFMFCLLLLSVG VGVYLLPNR

Design24.mosaic2 Amino Acid Sequence SEQ ID NO: 29 MSTNPKPQRKIKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRAPRKT SERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRG SRPSWGPTDPRRRSRNLGKVIDTLTCGLADLMGYIPLVGAPLGGAAKALAHGV RVLEDGVNYATGNIPGCSFSIFLLALLSCLTTPASAYEVRNASGAYHVTNDCSN SSIVYETADMIMHTPGCVPCVREGNSSRCWVALTPTLAARNASIPTTAIRRHVD LLVGTAAFCSAMYVGDLCGSVFLVSQLFTFSPRRHVTLQDCNCSIYPGHVSGH RMAWDMIMNWSPTTALVVSQLLRIPQAIVDMVAGAHWGVLVGLAYYSMVGNW AKVLVVMLLFAGVDGTTHVSGAQAGHATRSFTSLFTLGASQKVQLINTNGSWHI NRTALNCNDSLQTGFLAALFYTHKFNASGCPERMASCRSIDKFDQGWGPITYA EPHDLDQRPYCWHYAPRPCGIVPASEVCGPVYCFTPSPVVVGTTDRSGAPTY RWGENETDVLLLNNTRPPHGNWFGCTWMNSTGFTKTCGGPPCNIGGAGNNT LTCPTDCFRKHPEATYTRCGSGPWLTPRCMVDYPYRLWHYPCTFNFTIFKIRM YVGGVEHRLDAACNWTRGERCDLDDRDRSELSPLLLSTTEWQILPCSFTTLPA LSTGLIHLHQNVVDVQYLYGIGSAVVSFVIKWEYVVLLFLLLADARICACLWMML LIAQAEAALENLVVLNAASVAGAHGFLSFLVFFCAAWYVKGRLVPGAAYALYGV WPLLLLLLALPPRAYAMDREMAASCGGAVFIGLALLTLSPYYKVFLAKLIWWLQ YFITRAEAHLHVWVPPLNVRGGRDAIILLMCAVHPELIFDITKILLAIFGPLMVLQA GLTRVPYFVRAQGLIRVCMLVRKVAGGHYIQMALMKLAALTGTYVYNHLTPLRD WAHAGLRDLVVAVEPVVFSDMETKIITWGADTAACGDIILGLPVSARRGREILLG PADSLEGRGWRLLAPITAYAQQTRGLFGCIITSLTGRDKNQVEGEVQVVSTATQ SFLATCINGVCWTVYHGAGTKTLAGPKGPVTQMYTNVDQDLVGWQAPPGARS LSPCTCGSSDLYLVTRHADVIPVRRRGDNRGSLLSPRPVSYLKGSSGGPLLCP SGHAVGIFRAAVCTRGVAKAVDFVPVESMETTTRSPVFTDNSSPPAVPQTFQV SHLHAPTGSGKSTKVPAAYATQGYKVLVLNPSVAATLGFGAYMSKAYGTDPNI RTGVRTITTGAPITYSTYGKFLADGGCSGGAYDIIMCDECHSTDSTSILGIGTVLD QAETAGARLVVLATATPPGSVTVPHPNIEEIALSNTGEIPFYGKAIPIEAIKGGRH LIFCHSRKKCDELAAKLSGLGINAVAYYRGLDVSVIPASGNVVVVATDALMTGFT GDFDSVIDCNTCVVQTVDFSLDPTFTIDTTTVPQDAVSRSQRRGRTGRGRRGIY RFVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETTVRLRAYLNTPGLPVC QDHLEFWEGVFTGLTHIDAHFLSQTKQAGENFPYLTAYQATVCARALAPPPSW DQMWKCLVRLKPTLHGPTPLLYRLGAVQNEVILTHPITKYIMACMSADLEWTS TWVLVGGVLAALAAYCLTAGSWIVGRIVLSGRPAWPDREVLYREFDEMEECA SQLPYIEQGMQLAEQFRQKALGLLQTATKQAEAAVPVVESKWRALEAFWAKH MWNFISGVQYLAGLSTLPGNPAIASLMAFTASITSPLTTQYTLLFNILGGWVAAQ LAPPSAASAFVGAGIAGAAVGSIGLGKVLVDVLAGYGAGVAGALVAFKVMSGE VPSTEDLVNLLPAILSPGALVVGWCAAILRRHVGPGEGAVQWMNRLIAFASRG NHVSPTHYVPESDAAVRVTQILSSLTITQLLRRLHQWINEDCSTPCSGSWLRDV WDWICTVLTDFKTWLQSKLLPRLPGIPFFSCQRGYRGVWRGDGVMQTTCPCG AQIAGHVKNGSMKIVGPKTCSNTWHGTFPINAYTTGPCTPSPAPNYTRALWRV AAEDYVEVTRVGDFHYVTGMTTDNVKCPCQVPAPEFFSEVDGVRLHRYAPAC RPLLREEVTFQVGLNQYWGSQLPCEPEPDVTVLTSMLTDPSHITAEAAKRRLA RGSPPSLASSSASQLSAPSLKATCTTRHDSPDADLIEANLLWRQEMGGNITRVE SENKWILDSFEPLRAEEDEREISVPAEILRKSRKFPRAMPIWARPDYNPPLIES WKDPDYAPPVVHGCPLPPTKAPPIPPPRRKRTWLTESTVSSALAELATKTFGS SESSAVDSGTASAPPDQPSDNGDTGSDVESYSSMPPLEGEPGDPDLSDGSW STVSGEAGEDVVCCSMSYTWTGALITPCAAEENKLPINALSNSLLRHHNMVYAT TSRSAGLRQKKVTFDRQQVLDDHYRDVLKEIKAKASTVKAKLLSVEEACKLTPP HSARSKFGYGAKDVRNLSSKAVNHIHSVWKDLLEDTVTPIDTTIMAKNEVFCVQ PEKGGRKPARFIVFPDLGVRVCEKMALYDVVSTLPQAVMGASYGFQYSPSQR VEFLVNAWKSKKNPMGFAYDTRCFDSTVTESDIRVEESIYQCCDLAPEARQAIK SLTERLYIGGPMTNSKGQNCGYRRCRASGVLTTSCGNTITCYLKASAACRAAK LQDCTMLVNGDDLVVICESAGTQEDAAALRAFTEAMTRYSAPPGDPPRPEYDL ELITSCSSNVSVAHDASGKRVYYLTRDPTTPLARAAWETARHTPINSWLGNIIMY APTLWARMVLMTHFFSILIAQEQLEKALDCQIYGACYSIEPLDLPQIIERLHGLSA FTLHSYSPGEINRVASCLRKLGVPPLRVWRHRARSVRARLLSQGGRAATCGKY LFNWAVRTKLKLTPIPAASRLDLSGWFVAGYGGGDIYHSLSRARPRWFMLCLLL LSVGVGVYLLPNR

Design24.mosaic3 Amino Acid Sequence SEQ ID NO: 30 MSTNPKPQRQTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPKLGVRATRKT SERSQPRGRRQPIPKARHPEGRAWAQPGYPWPLYGNEGMGWAGWLLSPRG SRPNWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGVARALAHGV RVVEDGVNYATGNLPGCSFSIFLLALLSCLTIPASAHEVRNASGVYHVTNDCSN SSIVYEAADVIMHTPGCVPCVREDNSSRCWVALTPTLAARNSSVPTTTIRRHVD LLVGAAAFCSVMYVGDLCGSVFLISQLFTFSPRRYETVQDCNCSLYPGHVSGH RMAWDMMMNWSPTTALWSQLLRIPQAVMDMVAGAHWGVLAGLAYYSMVG NWAKVLIVLLLFAGVDGNTRVSGGEAAKNTMGFASLFVSGPSQKIQLINTNGSW HINRTALNCNDSLHTGFLAALFYAHKFNSSGCPERMASCRPIDEFAQGWGPITH GVPDNLDQRPYCWHYAPQPCGTIPAAQVCGPVYCFTPSPVVVGTTDRFGAPT YNWGENETDVLILNNTRPPQGNWFGCTWMNSTGFTKTCGAPPCNIGGVGNNT LVCPTDCFRKHPEATYTKCGSGPWLTPRCLVDYPYRLWHYPCTVNFSIFKVRM YVGGVEHRLSAACNWTRGERCNVEDRDRSELSPLLLSTTEWQVLPCSFTTLPA LSTGLIHLHQNIVDVQYLYGVGSAVVSVAIRWEYVVLLFLLLADARFCACLWMM LLVAQAEAALENLVVLNAASVAGAFIGILPFLVFFCAAVVYIKGKLVPGAAYAIYGV WPLLLLLLTLPPRAYAMDREVAASCGGAVFVGLVLLTLSPHYKVFLARLIWWLQ YLITRAEALLQVWVPPLNVRGGRNAIILLTCWHPELIFEITKTLLAILGPLTVLQV GLTKVPYFVRAQGLIRACMLVRKAAGGHYVQMAFVKLAALTGTYVYDHLTPLQ DWAHAGLRDLAVAVEPVVFSAMETKIITWGAETAACGDIISSLPVSARRGRELLL GPADSFEGQGWRLLAPITAYAQQTRGLLGCIVTSLTGRDKNQVEGEAQWSTA TQSFLATCINGACWTVFHGAGSKTLAGPKGPIIQMYTNVDQDLVGWAAPPGAR SLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPGPISYLKGSSGGPLLCP SGHAVGVFRAAVCTRGVAKAVDFVPVESMETTMRSPVFTDNSTPPAVPQTFQ VAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGVDPN IRTGVRTITTGASITYSTYGKFLADGGCSGGAYDIIMCDECHSTDATTILGVGTVL DQAETAGARLWLATATPPGSVTVPHSNIEEVALSNTGEIPFYGKAIPLETIKGG RHLIFCHSRKKCDELAAKLSALGVNAVAYYRGLDVSVIPASGDVWVATDALMT GYTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRAQRRGRTGRGR AGIYRFVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETSVRLRAYLNTPGL PVCQDHLEFWESVFTGLTHIDAHFLSQTKQAGDNFPYLTAYQATVCARSQAPP PSWDQMWKCLLRLKPTLHGPTPLLYRLGAVQNEITLTHPITKFIMACMSADLEV VTSTWVLVGGVLAALAAYCLTTGSVVIVGRIILSGRPAVIPDREVLYREFDEMEE CATHLPYIEQGMQLAEQFKQKALGLLQTASKQAEAAAPVMESKWRALETFWAK HMWNFISGIQYLAGLSTLPGNPAIASLMAFTASVTSPLTTQSTLLFNILGGWVAA QLAPPSAASAFVGAGIVGAAVGSIGLGRVLVDILAGYGAGVAGALVAFKVMSGD MPSTEDLVNLLPAILSPGALWGVVCAAILRRHVGPGEGAVQWMNRLIAFASRG NHVSPTHYVPESDAAARVTQILSNLTITQLLKRLHQWINEDCSTPCSGSWLRDV WDWICTVLADFKTWLQSKLLPRLPGVPFFSCQRGYKGIWRGDGIMHTTCSCG AQITGHVKNGSMRIVGPRTCSNTWHGTFPINAYTTGSCTPSPAPNYSKALWRV AAEEYVEVTRVGDFHYVTGVTTDNIKCPCQVPAPEFFTELDGVRLHRYAPACK PLLRDEVTFQVGLNQYTVGSQLPCEPEPDVTWTSMLTDPSHITAEAARRRLAR GSPPSLASSSASQLSALSLKATCTTHHGAPDTDLIEANLLWRQEMGGNITRVES ENKVVVLDSFEPLRAEEDEREPSVPAEILRKTRKFPAAMPVWARPDYNPPLLES WKNPDYVPPVVHGCPLPPTKTPPIPPPRRKKTWLTESTVSSALAELAVKAFGS SGSSAADSGTATAPPGQPSDCGDTGSDAESYSSMPPLEGEPGDPDFSDGSW STVSEEAGEDWCCSMSYTWTGALITPCAAEESKLPINALSNSLLRHHSMVYST TSRSASQRQKKVTFDRLQVLDDHYQDVLKEMKAKASTVKARLLSVEEACRLTP PHSARSKFGYGAKDVRNLSGKAVNHIRSVWKDLLEDTDTPIDTTIMAKNEVFCI QPEKGGRKPARLIVYPDLGVRVCEKMALYDVVSTLPQAVMGPSYGFQYSPGQ RVEFLVNAWKSKKCPMGFAYDTRCFDSTVTENDIRVEESIYQSCDLAPEARQAI RSLTERLYIGGPLTNSKGQSCGYRRCRASGVLTTSCGNTLTCYLKASAACRAA KLRDCTMLVCGDDLWICESAGTQEDAANLRVFTEAMTRYSAPPGDPPQPEYD LELITSCSSNVSVARDASGKRVYYLTRDPTTPIARAAWETARHTPVNSWLGNIIM YAPTLWARMILMTHFFSILLAQEQLEKALDCQIYGATYSIEPLDLPQIIQRLHGLS AFSLHSYSPGEINRVAACLRKLGVPPLRVWRHRARSVRAKLLSRGGRAATCGR YLFNWAVKTKLKLTPIPAASQLDLSGWFVAGYSGGDIYHSVSRARPRWFMWCL LLLSVGVGIYLLPNR

Design24.mosaic4 Amino Acid Sequence SEQ ID NO: 31 MSTNPKPQRRTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRAIRKT SERSQPRGRRQPIPKARRPEGRAWAQPGYPWPLYGNEGLGWAGWLLSPRG SRPSWGPSDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGGPLGGAARALAHGV RVLEDGVNYATGNMPGCSFSIFLLALLSCLTIPASAYEVRNVSGIYHVTNDCSNA SIVYEAADMIMHTPGCVPCVRESNFSRCWVALTPTLAARNSSIPTTTIRRHVDLL VGAAALCSAMYVGDLCGSVLLVSQLFTFSPRRHETVQDCNCSIYPGHLSGHRM AWDMMMNWSPTAALVVSQLLRIPQAVVDMVVGAHWGVLAGLAYYSMVGNWA KVLIVMLLFAGVDGHTHVTGGRVASSTQSLVSWLSQGPSQKIQLVNTNGSWHI NRTALNCNDSLQTGFIAALFYAHRFNASGCPERMASCRPIDKFAQGWGPITHV VPNISDQRPYCWHYAPQPCGIVPASQVCGPVYCFTPSPVVVGTTDRSGVPTYS WGENETDVLLLNNTRPPQGNWFGCTWMNGTGFTKTCGGPPCNIGGVGNNTLI CPTDCFRKHPEATYAKCGSGPWLTPRCIVDYPYRLWHYPCTVNFTVFKVRMY VGGVEHRLNAACNWTRGERCDLEDRDRSELSPLLLSTTEWQILPCAFTTLPAL STGLIHLHRNIVDVQYLYGIGSAVVSFAIKWEYILLLFLLLADARVCSCLWMMLL AQAEATLENLVVLNAASVAGTHGILSLLVFFCAAVVYIKGRLVPGAAYAFYGVWP LLLLLLALPPRAYAMEREMAASCGGGVFVGLVLLTLSPYYKVFLARLIWWLQYLI TRAEAHLQVWVPPLNVRGGRDAIILLTCAVHPELIFDITKLLLAILGPLMVLQAGIT RVPYFVRAQGLLRACMLVRKVAGGHYVQMAFMKLAALTGTYVYDHLTPLRDW AHVGLRDLAVAVEPVVFSDMETKLITWGADTAACGDIISGLPVSARRGKEILLGP ADSFGEQGWRLLAPITAYSQQTRGLLGCIITSLTGRDKNQVDGEVQVLSTATQS FLATCVNGVCWTVYHGAGSKTLAGPKGPITQMYTNVDQDLVGWPAPPGARSM TPCTCGSSDLYLVTRHADWPVRRRGDSRGSLLSPRPISYLKGSSGGPLLCPS GHWGIFRAAVCTRGVAKAVDFVPVESLETTMRSPVFTDNSSPPTVPQSYQVA HLHAPTGSGKSTRVPAAYAAQGYKVLVLNPSVAATLSFGAYMSKAHGTDPNIR TGVRTITTGSPITYSTYGKFLADGGCSGGAYDIIICDECHSTDSTTVLGIGTVLDQ AETAGVRLTVLATATPPGSVTVPHPNIEEVALSTTGEIPFYGKAIPIEVIKGGRHLI FCHSKKKCDELAAKLSSLGLNAVAYYRGLDVSVIPSSGDVVVVATDALMTGYTG DFDSVIDCNTCVIQTVDFSLDPTFTIETTTVPQDAVSRTQRRGRTGRGRGGIYR FVTPGERPSGMFDSSVLCECYDAGCAWYELTPAVTSVRLRAYLNTPGLPVCQ VHLEFWESVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARAKAPPPSWD QMWKCLIRLKPTLHGSTPLLYRLGAVQNEVTLTHPITKYIMTCMSADLEVATST WVLVGGVLAALAAYCLTTGSVVIVGRIILSGKPAVIPDREVLYKEFDEMEECASH LPYIEQGVQLAEQFKQKALGLLQTATKQAEAAAPWESKWQALEAFWAKHMW NFISGIQYLAGLSTLPGNPAIASLMAFTASITSPLTTQNTLLFNILGGWVAAQLAP PSAASAFVGAGIVGAAVGSVGLGKVLVDILAGYGAGVAGALVAFKVMSGEMPS TEDLVNLLPAILSPGALWGWCAAVLRRHVGPGEGAVQWMNRLIAFASRGNH VSPTHYVPESDAAARVTQILSGLTITQLLKRLHQWINEDCSTPCSGSWLKDVWD WICTVLSDFKTWLQSKLLPRLPGLPFLSCQRGYKGVWRGDGIMQTTCPCGAQI TGHVKNGSMRIVGPKTCSNMWHGTFPINAYTTGPCTPSPAPNYSRALWRVAA EEYVEITRVGDFHYVTGMTTDNLKCPCQVPAPEFFTEVDGVRLHRYAPVCKPL LREEVVFQVGLNQYPVGSQLPCEPEPDVAVLTSMLTDPSHITAETAKRRLARG SPPSLARSSASQLSAPSLKATCTTHHDSPDADLIEANLLWRQAMGGNITRVESE NKVVILDSFDPLHAEEDEREVSVAAEILRKSRKFPPALPIWARPDYNPPLLESWK DPDYVPPWHGCPLPPTKAPPVPPPRRKRTIVLTESTVSSALAELATKTFGSSG SSAVDSGTATAPPDQASDDGDKGSDVESYSSMPPLEGEPGDPDLSDGSWST VSSDGGTEDWCCSMSYSWTGALITPCAAEESKLPINPLSNSLLRHHNLVYSTT SRSASLRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKARLLSIEEACKLTPPH SAKSKFGYGAKDVRNLSSRAVNHIRSVWEDLLEDTETPIDTTIMAKSEVFCVQP EKGGRKPARLIVFPDLGVRVCEKMALYDWSTLPQAVMGSSYGFQYSPKQRVE FLVNTWKSKKCPMGFSYDTRCFDSTVTENDIRTEESIYQCCDLAPEARQAIRSL TERLYVGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKATAACRAAKLQ DCTMLVCGDDLVVICDSAGTQEDAASLRVFTEAMTRYSAPPGDLPQPEYDLELI TSCSSNVSVAYDASGKRVYYLTRDPSTPLARAAWETVRHTPVNSWLGNIIMYA PTLWARMILMTHFFSILLAQEQLGKALDCQIYGACYSIEPLDLPLIIQRLHGLSAF SLHSYSPGEINRVASCLRKLGVPPLRAWRHRARSVRATLLSQGGRAAICGKYL FNWAVKTKLKLTPIPAASQLDLSNWFVAGYNGGDIYHSLSRARPRWIMWCLLLL SVGVGIYLLPNR

Design25.mosaic1 Amino Acid Sequence SEQ ID NO: 32 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGMGWAGWLLSPRG SRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGV RVLEDGVNYATGNLPGCSFSIFLLALLSCLTIPASAYEVRNVSGVYHVTNDCSN SSIVYEAADMIMHTPGCVPCVRENNSSRCWVALTPTLAARNASVPTTTIRRHVD LLVGAAAFCSAMYVGDLCGSVFLVSQLFTFSPRRHETVQDCNCSIYPGHITGHR MAWDMMMNWSPTTALVVSQLLRIPQAVVDMVAGAHWGVLAGLAYYSMVGN WAKVLIVMLLFAGVDGHTHVTGGRVASSTQSLVSWLSQGPSQKIQLINTNGSW HINRTALNCNDSLQTGFLAALFYTHKFNASGCPERMASCRPIDEFAQGWGPITY AEPGSSDQRPYCWHYAPRPCGIVPASQVCGPVYCFTPSPVVVGTTDRFGVPT YSWGENETDVLLLNNTRPPQGNWFGCTWMNSTGFTKTCGGPPCNIGGVGNN TLTCPTDCFRKHPEATYTKCGSGPWLTPRCLVDYPYRLWHYPCTVNFTIFKVR MYVGGVEHRLNAACNWTRGERCDLEDRDRSELSPLLLSTTEWQILPCSFTTLP ALSTGLIHLHQNIVDVQYLYGVGSSIASWAIKWEYVVLLFLLLADARVCACLWM MLLIAQAEAALENLVVLNAASVAGAFIGILSFLVFFCAAVVYIKGRLVPGAAYALYG VWPLLLLLLALPPRAYAMDREMAASCGGAVFVGLVLLTLSPYYKVFLARLIWWL QYFITRAEAHLQVWVPPLNVRGGRDAIILLTCAVHPELIFDITKLLLAILGPLMVLQ AGITRVPYFVRAQGLIRACMLVRKVAGGHYVQMAFMKLAALTGTYVYDHLTPL RDWAHAGLRDLAVAVEPWFSDMETKIITWGADTAACGDIILGLPVSARRGREIL LGPADSLEGQGWRLLAPITAYAQQTRGLLGCIITSLTGRDKNQVEGEVQVVSTA TQSFLATCINGVCWTVYHGAGSKTLAGPKGPITQMYTNVDQDLVGWQAPPGA RSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPLLC PSGHAVGIFRAAVCTRGVAKAVDFIPVESMETTMRSPVFTDNSSPPAVPQTFQ VAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGVDPN IRTGVRTITTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGTVLD QAETAGARLVVLATATPPGSVTVPHPNIEEVALSTTGEIPFYGKAIPIETIKGGRH LIFCHSKKKCDELAAKLSGLGLNAVAYYRGLDVSVIPTSGDVVVVATDALMTGF TGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGRRGI YRFVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETSVRLRAYLNTPGLPVC QDHLEFWESVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARAQAPPPSW DQMWKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMACMSADLEWTST WVLVGGVLAALAAYCLTTGSVVIVGRIILSGKPAIIPDREVLYREFDEMEECASHL PYIEQGMQLAEQFKQKALGLLQTATKQAEAAAPWESKWRALEAFWAKHMWN FISGIQYLAGLSTLPGNPAIASLMAFTASITSPLTTQHTLLFNILGGWVAAQLAPP SAASAFVGAGIAGAAVGSIGLGKVLVDILAGYGAGVAGALVAFKIMSGEVPSTE DLVNLLPAILSPGALWGWCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVSP THYVPESDAAARVTQILSSLTITQLLKRLHQWINEDCSTPCSGSWLRDVWDWIC TVLTDFKTWLQSKLLPRLPGVPFFSCQRGYKGVWRGDGIMQTTCPCGAQITGH VKNGSMRIVGPKTCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAAEEYV EVTRVGDFHYVTGMTTDNVKCPCQVPAPEFFTEVDGVRLHRYAPACKPLLREE VTFQVGLNQYLVGSQLPCEPEPDVAVLTSMLTDPSHITAETAKRRLARGSPPSL ASSSASQLSAPSLKATCTTHHDSPDADLIEANLLWRQEMGGNITRVESENKVVI LDSFDPLRAEEDEREVSVPAEILRKSRKFPPALPIWARPDYNPPLLESWKDPDY VPPWHGCPLPPTKAPPIPPPRRKRTWLTESTVSSALAELATKTFGSSESSAV DSGTATAPPDQPSDDGDAGSDVESYSSMPPLEGEPGDPDLSDGSWSTVSEE ASEDVVCCSMSYTWTGALITPCAAEESKLPINALSNSLLRHHNMVYATTSRSAS QRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSVEEACKLTPPHSARS KFGYGAKDVRNLSSKAVNHIRSVWKDLLEDTETPIDTTIMAKNEVFCVQPEKGG RKPARLIVFPDLGVRVCEKMALYDVVSTLPQAVMGSSYGFQYSPGQRVEFLVN AWKSKKTPMGFSYDTRCFDSTVTESDIRVEESIYQCCDLAPEARQAIRSLTERL YIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKASAACRAAKLQDCTM LVCGDDLWICESAGTQEDAASLRVFTEAMTRYSAPPGDPPQPEYDLELITSCS SNVSVAHDASGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMYAPTLW ARMILMTHFFSILLAQEQLEKALDCQIYGACYSIEPLDLPQIIQRLHGLSAFSLHSY SPGEINRVASCLRKLGVPPLRVWRHRARSVRAKLLSQGGRAATCGKYLFNWA VRTKLKLTPIPAASQLDLSGWFVAGYSGGDIYHSLSRARPRWFMWCLLLLSVG VGIYLLPNR

Design26.mosaic1 Amino Acid Sequence Amino Acid Sequence SEQ ID NO: 33 MSTNPKPQRKTKRNTNRRPQDVKFPGGGKIVGGVYLLPRRGPRLGVRAPRKT SERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRG SRPSWGPNDPRRRSRNLGKVIDTLTCGLADLMGYIPLVGAPLGGAARALAHGV RVLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSTGLYHVTNDCPN SSIVYEAADAILHTPGCVPCVREGNASRCWVAMTPTVATRDGKLPTTQLRRHID LLVGSATLCSALYVGDLCGSVFLVGQLFTFSPRRHWTTQDCNCSIYPGHITGHR MAWDMMMNWSPTTALVVAQLLRIPQAILDMIAGAHWGVLAGIAYFSMVGNWA KVLVVLLLFAGVDAETHVTGGSAAKDTSGFTSLFRIGARQNIQLINSNGSWHINR TALNCNDSLQTGFLAALFYTHKFNSSGCPERLASCRPLTDFAQGWGPISYANG SGPDQRPYCWHYPPKPCGIVPAKSVCGPVYCFTPSPVVVGTTDRSGAPTYNW GENDTDVFVLNNTRPPLGNWFGCTWMNSSGFTKVCGAPPCVIGGVGNNTLHC PTDCFRKHPEATYSRCGSGPWITPRCLVHYPYRLWHYPCTINYTIFKVRMYVG GVEHRLEAACNWTRGERCNLEDRDRSELSPLLLSTTQWQVLPCSFTTLPALST GLIHLHQNVVDVQYLYGVGSSIASWAIKWEYVVLLFLLLADARVCSCLWMMLLI SQAEAALENLVILNAASLAGTHGLVSFLVFFCFAWYLKGRWVPGAVYALYGMW PLLLLLLALPQRAYALDTEVAASCGGVVLVGLMALTLSPYYKRYISWCLWWLQY FLTRVEAQLHVWVPPLNVRGGRDAVILLMCVVHPTLVFDITKLLLAVFGPLWILQ ASLLKVPYFVRVQGLLRICALARKMAGGHYVQMAIIKLGALTGTYVYNHLTPLRD WAHNGLRDLAVAVEPVVFSQMETKLITWGADTAACGDIINGLPVSARRGREILL GPADGMVSKGWRLLAPITAYAQQTRGLLGCIVTSLTGRDKNQVEGEVQIVSTA AQTFLATCINGVCWTVYHGAGTRTIASPKGPVIQMYTNVDKDLVGWPAPQGAR SLTPCACGSSDLYLVTRHADVIPVRRRGDGRGSLLSPRPVSYLKGSSGGPLLC PSGHAVGIFRAAVCTRGVAKAVDFVPVESMETTMRSPVFTDNSSPPAVPQTFQ VAHLHAPTGSGKSTRVPAAYAAQGYKVLVLNPSVAATLSFGAYMSKAHGVDPN IRTGVRTITTGAPITYSTYGKFLADGGCSGGAYDIIMCDECHSTDSTTILGIGTVL DQAETAGARLVVLATATPPGSITVPHPNIEEVALSNTGEIPFYGKAIPIETIKGGR HLIFCHSRKKCDELAAKLSGLGLNAVAYYRGLDVSVIPASGDVVVVATDALMTG FTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGRR GIYRFVTPGERPSGMFDSSVLCECYDAGCAVVYELTPAETTVRLRAYMNTPGLP VCQDHLEFWEGVFTGLTHIDAHFLSQTKQSGENLPYLVAYQATVCARAQAPPP SWDQMWKCLIRLKPTLHGSTPLLYRLGAVQNEITLTHPVTKYIMTCMSADLEW TSTWVLVGGVLAALAAYCLSTGCVVIVGRIVLSGKPAIIPDREVLYREFDEMEEC SQHLPYIEQGMMLAEQFKQKALGLLQTASRQAEVIAPAVQTNWQKLEAFWAKH MWNFISGVQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTSQTLLFNILGGWVAA QLAAPGAATAFVGAGLAGAAIGSVGLGKVLVDIIAGYGAGVAGALVAFKIMSGE VPSTEDLVNLLPAILSPGALVVGVVCAAVLRRHVGPGEGAVQWMNRLIAFASR GNHVSPTHYVPESDAAARVTAILSSLTVTQLLRRLHQWISSECTTPCSGSWLRD IWDWICEVLSDFKTWLKAKLMPQLPGIPFVSCQRGYRGVWRGDGIMHTRCHC GAEITGHVKNGTMRIVGPRTCRNMWSGTFPINAYTTGPCTPLPAPNYTFALWR VSAEEYVEIRQVGDFHYVTGMTTDNLKCPCQVPSPEFFTELDGVRLHRFAPPC KPLLREEVSFRVGLHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAGRRLA RGSPPSVASSSASQLSAPSLKATCTANHDSPDAELIEANLLWRQEMGGNITRV ESENKVWLDSFDPLVAEEDEREISVPAEILRKSRRFAPALPIWARPDYNPPLLE TWKKPDYEPPWHGCPLPPPQSPPVPPPRKKRTWLTESTVSTALAELATKSF GSSSTSGITGDNTTTSSEPAPSGCPPDSDAESYSSMPPLEGEPGDPDLSDGS WSTVSSGADTEDWCCSMSYSWTGALVTPCAAEEQKLPINALSNSLLRHHNLV YSTTSRSACQRQKKVTFDRLQVLDSHYQDVLKEVKAAASKVKANLLSVEEACS LTPPHSAKSKFGYGAKDVRCHARKAVNHINSVWKDLLEDSVTPIDTTIMAKNEV FCVQPEKGGRKPARLIVYPDLGVRVCEKMALYDVVSKLPLAVMGSSYGFQYSP GQRVEFLVQAWKSKKTPMGFSYDTRCFDSTVTESDIRTEEAIYQCCDLDPQAR VAIKSLTERLYVGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKARAACR AAGLQDCTMLVCGDDLWICESAGVQEDAASLRAFTEAMTRYSAPPGDPPQPE YDLELITSCSSNVSVAHDGAGKRVYYLTRDPTIPLARAAWETARHTPVNSWLG NIIMFAPTLWARMILMTHFFSVLIARDQLEQALDCEIYGACYSIEPLDLPPIIQRLH GLSAFSLHSYSPGEINRVAACLRKLGVPPLRAWRHRARSVRARLLSRGGRAAI CGKYLFNWAVRTKLKLTPIAAAGQLDLSGWFTAGYSGGDIYHSVSHARPRWF WFCLLLLAAGVGIYLLPNR

Design26.mosaic2 Amino Acid Sequence SEQ ID NO: 34 MSTNPKPQRRTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERSQPRGRRQPIPKARQPEGRAWAQPGYPWPLYGNEGMGWAGWLLSPRG SRPSWGPTDPRRRSRNLGRVIDTLTCGFADLMGYIPLVGAPLGGVARALAHGV RVVEDGVNYATGNLPGCSFSIFLLALLSCLTIPASAYEVRNVSGVYHVTNDCSN SSIVYEAADMIMHTPGCVPCVRENNSSRCWVALTPTLAARNASVPTTTIRRHVD LLVGAAAFCSAMYVGDLCGSVFLVSQLFTFSPRRHETVQDCNCSIYPGHVSGH RMAWDMMMNWSPTAALVVSQLLRIPQAVVDMVAGAHWGVLAGLAYYSMVGN WAKVLIVMLLFAGVDGHTHVTGGRVASSTQSLVSWLSQGPSQKIQLVNTNGS WHINRTALNCNDSLNTGFLAALFYTHSFNASGCPERMASCRPIDKFDQGWGPI TYAEPGSSDQRPYCWHYAPRPCGIVPASQVCGPVYCFTPSPVVVGTTDRFGV PTYSWGENETDVLLLNNTRPPQGNWFGCTWMNSTGFTKTCGGPPCNIGGVG NNTLTCPTDCFRKHPEATYTKCGSGPWLTPRCLVDYPYRLWHYPCTVNFTIFK VRMYVGGVEHRLNAACNWTRGERCDLEDRDRSELSPLLLSTTEWQILPCSFTT LPALTTGLIHLHQNIVDVQYLYGIGSAVVSFAIKWEYVLLLFLLLADARVCACLWM MLLIAQAEAALENLVVLNAASVAGAFIGILSFLVFFCAAVVYIKGRLVPGAAYALYG VWPLLLLLLALPPRAYAMDREMAASCGGAVFVGLALLTLSPHYKVFLARLIWWL QYFITRAEAHLQVWIPPLNVRGGRDAIILLTCAVHPELIFDITKLLLAILGPLMVLQ AGITRVPYFVRAQGLIRACMLVRKVAGGHYVQMAFMKLAALTGTYVYDHLTPL RDWAHAGLRDLAVAVEPWFSDMETKIITWGADTAACGDIILGLPVSARRGKEIL LGPADSLEGQGWRLLAPITAYSQQTRGLLGCIITSLTGRDKNQVEGEVQVVSTA TQSFLATCVNGVCWTVYHGAGSKTLAGPKGPITQMYTNVDQDLVGWQAPPGA RSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPLLC PAGHAVGIFRAAVCTRGVAKAVDFIPVENLETTMRSPVFTDNSSPPAVPQSFQV AHLHAPTGSGKSTKVPAAYAAQGYTVLVLNPSVAATLGFGAYMSKAHGIDPNIR TGVRTITTGSPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGTVLDQ AETAGVRLTVLATATPPGSVTVPHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHL IFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVATDALMTGYTG DFDSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKPGIYR FVAPGERPSGMFDSSILCECYDAGCAWYELTPAETSVRLRAYLNTPGLPVCQD HLEFWESVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARAQAPPPSWDQ MWKCLTRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMACMSADLEVVTSTW VLVGGVLAALAAYCLTTGSVVIVGRIILSGKPAVIPDREVLYQEFDEMEECASHL PYIEQGMQLAEQFKQKALGLLQTATKQAEAAAPWESKWRALETFWAKHMWN FISGIQYLAGLSTLPGNPAIASLMAFTASITSPLTTQHTLLFNILGGWVAAQLAPP SAASAFVGAGIAGAAVGSIGLGKVLVDILAGYGAGVAGALVAFKVMSGEMPSTE DLVNLLPAILSPGALWGWCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVSP THYVQESDAAARVTQILSSLTITQLLKRLHQWINEDCSTPCSGSWLRDVWDWIC TVLTDFKTWLQSKLLPRLPGVPFFSCQRGYKGVWRGDGIMQTTCPCGAQITGH VKNGSMRIVGPKTCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAAEEYV EVTRVGDFHYVTGMTTDNVKCPCQVPAPEFFTEVDGVRLHRYAPACKPLLREE VTFQVGLNQYLVGSQLPCEPEPDVTVLTSMLTDPSHITAETAKRRLARGSPPSL ASSSASQLSAPSLKATCTTHHDSPDADLIEANLLWRQEMGGNITRVESENKVVI LDSFDPLRAEEDEREVSVPAEILRKSRKFPPALPVWARPDYNPPLLESWKDPD YVPPVVHGCPLPPTKAPPIPPPRRKRTVVLTESTVSSALAELATKTFGSSESSAV DSGTATAPPDQPSDDGDAGSDVESYSSMPPLEGEPGDPDLSDGSWSTVSEE ASEDVVCCSMSYTWTGALITPCAAEESKLPINALSNSLLRHHNMVYATTSRSAS QRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSVEEACKLTPPHSARS KFGYGAKDVRNLSSKAVNHIRSVWKDLLEDTETPIDTTIMAKSEVFCVQPEKGG RKPARLIVFPDLGVRVCEKMALYDWSTLPQAVMGSSYGFQYSPKQRVEFLVN AWKSKKCPMGFAYDTRCFDSTVTENDIRVEESIYQCCDLAPEARQAIRSLTERL YIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKASAACRAAKLQDCTM LVNGDDLWICESAGTQEDAASLRVFTEAMTRYSAPPGDPPKPEYDLELITSCS SNVSVAHDASGKRVYYLTRDPTTPLARAAWETARHTPINSWLGNIIMYAPTLWA RMILMTHFFSILLAQEQLEKALDCQIYGACYSIEPLDLPQIIERLHGLSAFSLHSYS PGEINRVASCLRKLGVPPLRVWRHRARSVRAKLLSQGGRAATCGKYLFNWAV KTKLKLTPIPAASQLDLSGWFVAGYSGGDIYHSLSRARPRWFMWCLLLLSVGV GIYLLPNR

Design27.mosaic1 Amino Acid Sequence SEQ ID NO: 35 MSTNPKPQRQTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRAPRKT SERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGMGWAGWLLSPRG SRPSWGPSDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARVLAHGV RALEDGVNYATGNLPGCSFSIFLLALLSCLTIPASAYEVRNASGVYHVTNDCSN SSIVYETADSILHSPGCVPCVREGNSSRCWVALTPTLAARNSSIPTTTIRRHVDL LVGAAALCSAMYVGDLCGSVFLVSQLFTFSPRRYETVQDCNCSIYPGHVSGHR MAWDMIMNWSPTTALVVSQLLRIPQAVVDMVAGAHWGVLAGLAYYSMAGNW AKVLIVMLLFAGVDGHTHVTGGRVASSTQSLVSWLSQGPSQKIQLVNTNGSWH INRTALNCNDSLQTGFIAALFYTHRFNSSGCPERMASCRSIDKFDQGWGPITYA EPSNSDQRPYCWHYAPQPCGIVPASEVCGPVYCFTPSPWVGTTDRFGVPTY SWGENETDVLLLNNTRPPQGNWFGCTWMNSTGFTKTCGGPPCNIGGAGNNT LICPTDCFRKHPEATYTRCGSGPWLTPRCMVDYPYRLWHYPCTVNFTVFKVR MYVGGVEHRLNAACNWTRGERCDLEDRDRSELSPLLLSTTEWQILPCSFTTLP ALTTGLIHLHQNIVDVQYLYGVGSSIASWAIKWEYVILLFLLLADARICSCLWMML LISQAEAALENLVLLNAASLAGTHGLVSFLVFFCAAWYIKGRLVPGAAYALYGV WPLLLLLLTLPPRAYAMDREMAASCGGAVFVGLVLLTLSPHYKVFLARLIWWLQ YFITRAEAHLQVWIPPLNVRGGRDAIILLTCAIHPELIFTITKILLAILGPLMVLQAGI TRVPYFVRAQGLIRACMLVRKVAGGHYVQMAFMKLAALTGTYVYDHLTPLRDW AHAGLRDLAVAVEPVVFSDMETKIITWGADTAACGDIISGLPVSARRGKEILLGP ADSFGEQGWRLLAPITAYSQQTRGLFGCIITSLTGRDKNQVDGEVQVLSTATQS FLATCVNGVCWTVYHGAGSKTLAGPKGPITQMYTNVDQDLVGWPAPPGARSM TPCTCGSSDLYLVTRHADVIPVRRRGDGRGSLLSPRPVSYLKGSSGGPLLCPS GHWGIFRAAVCTRGVAKAVDFIPVESLETTMRSPVFTDNSSPPAVPQSFQVAH LHAPTGSGKSTKVPAAYATQGYKVLVLNPSVAATLGFGAYMSKAHGIEPNIRTG VRTITTGASITYSTYGKFLADGGCSGGAYDIIICDECHSTDSTTILGIGTVLDQAET AGARLVVLATATPPGSITVPHPNIEEVALSNTGEIPFYGKAIPLEAIKGGRHLIFCH SRKKCDELAAKLVALGVNAVAYYRGLDVSVIPTSGDWWATDALMTGFTGDF DSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRSQRRGRTGRGRGGIYRFV TPGERPSGMFDSSVLCESYDAGCAVVYELTPAETTVRLRAYLNTPGLPVCQDHL EFWESVFTGLTHIDAHFLSQTKQSGENFPYLVAYQATVCARAQALPPSWDQM WKCLVRLKPTLHGATPLLYRLGAVQNEVTLTHPVTKYIMTCMSADLEWTSTWV LVGGVLAALAAYCLTTGCVVIVGRVVLSGKPAVVPDREVLYQEFDEMEECASHL PYIEQGMQLAEQFKQKALGLLQIATKQAEAAAPVVESKWRALETFWAKHMWNF ISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTSQTLLFNILGGWVAAQLAAPG AATAFVGAGLAGAAIGSVGLGKVLVDIIAGYGAGVAGALVAFKIMSGEVPSTEDL VNLLPAILSPGALVVGVVCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTH YVPESDAAARVTQILSNLTITQLLKRLHQWINEDCSTPCSGSWLKDVWDWICTV LSDFKTWLQSKLLPRLPGVPFFSCQRGYKGVWRGDGIMQTTCPCGAQIAGHV KNGSMRIVGPRTCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAAEEYVE VTRVGDFHYVTGMTTDNVKCPCQVPAPEFFTEVDGVRLHRYAPACKPLLREEV TFQVGLNQYLVGSQLPCEPEPDVTWTSMLTDPSHITAEAARRRLARGSPPSLA SSSASQLSAPSLKATCTTRHDSPDADLIEANLLWRQAMGGNITRVESENKVVIL DSFEPLRAEEDEREVSVAAEILRKSKKFPPALPIWARPDYNPPLLESWKDPDYV PPWHGCPLPPAKAPPIPPPRRKRTWLTESTVSSALAELATKTFGSSESSAVD SGTATAPPDQPSDDGDAGSDVESYSSMPPLEGEPGDPDLSDGSWSTVSSEA GTEDVVCCSMSYTWTGALITPCAAEESKLPINPLSNSLLRHHSMVYSTTSRSAS LRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSIEEACKLTPPHSAKSK FGYGAKDVRSLSSRAVNHIRSVWEDLLEDTETPIDTTIMAKSEVFCVQPEKGGR KPARFIVFPDLGVRVCEKMALYDVVSTLPQAVMGPSYGFQYSPKQRVEFLVNT WKSKKCPMGFSYDTRCFDSTVTESDIRVEESIYQCCDLAPEARQAIKSLTERLYI GGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKATAACRAAKLQDCTML VNGDDLVVICESQGVQEDAANLRVFTEAMTRYSAPPGDLPQPEYDLELITSCSS NVSVAHDASGKRVYYLTRDPTTPLARAAWETVRHTPVNSWLGNIIMYAPTLWA RMVLMTHFFSILIAQEQLEKALDCQIYGACYSIEPLDLPQIIERLHGLSAFTLHSYS PGEINRVAACLRKLGVPPLRAWRHRARSVRARLLSQGGRAAICGKYLFNWAVK TKLKLTPIPAASQLDLSGWFVAGYSGGDIYHSLSRARPRWFMLCLLLLSVGVGV YLLPNR

Design27.mosaic2 Amino Acid Sequence SEQ ID NO 36 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERPQPRGRRQPIPKARQPEGRAWAQPGYPWPLYGNEGLGWAGWLLSPRG SRPSWGPTDPRRRSRNLGRVIDTLTCGFADLMGYIPLVGAPLGGVARALAHGV RVLEDSVNYATGNLPGCPFSIFLLALLSCLTTPASAYEVRNVSGVYHVTNDCSN ASIVYEAADMIMHTPGCVPCVRENNSSRCWVALTPTLAARNASVPTTTIRRHVD LLVGAAAFCSAMYVGDLCGSVFLISQLFTFSPRRHETVQDCNCSIYPGHVTGHR MAWDMMMNWSPTAALVVSQLLRIPQAVMDMVAGAHWGILAGLAYYSMVGNW AKVLIVLLLFAGVDGNTRVSGGEAAKNTMGFASLFVSGPSQKIQLINTNGSWHI NSTALNCNDSLNTGFLAALFYTHRFNASGCPERMASCRPIDEFAQGWGPITYT EPHDLDQRPYCWHYAPRPCGIVPASQVCGPVYCFTPSPVVVGTTDRSGAPTY NWGENDTDVFVLNNTRPPLGNWFGCTWMNSSGFTKVCGAPPCVIGGVGNNT LHCPTDCFRKHPEATYSRCGSGPWITPRCLVHYPYRLWHYPCTINYTIFKVRMY VGGVEHRLDAACNWTRGERCNLDDRDRSELSPLLLSTTQWQVLPCSFATLPA LSTGLIHLHQNVVDVQYLYGVGSSIVSWAIKWEYVVLLFLLLADARVCSCLWMM LLISQVEAALENLVILNAASLAGTHGLASFLVFFCFAWYLKGRWVPGAVYALYG MWPLLLLLLALPQRAYALDTEVAASCGGWLVGLMALTLSPYYKRYISWCLWW LQYFLTRVEAQLHVWVPPLNVRGGRDAVILLMCWHPTLVFDITKLLLAVFGPL WILQASLLKVPYFVRVQGLLRICALARKMAGGHYVQMAIIKLGALTGTYVYNHLT PLRDWAHNGLRDLAVAVEPVVFSQMETKLITWGADTAACGDIINGLPVSARRG QEILLGPADGMVSKGWRLLAPITAYAQQTRGLLGCIVTSLTGRDKNQVEGEVQI VSTAAQTFLATCINGVCWTVYHGAGTRTIASPKGPVIQMYTNVDKDLVGWPAP QGARSLTPCACGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGG PLLCPAGHAVGIFRAAVCTRGVAKAVDFIPVENLETTMRSPVFTDNSTPPAVPQ SYQVAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGVYMSKAHGI DPNIRTGVRTITTGSPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGT VLDQAETAGVRLTVLATATPPGSVTVPHSNIEEVALSTTGEIPFYGKAIPLEVIKG GRHLIFCHSKKKCDEVAAKLVALGINAVAYYRGLDVSVIPASGDVVVVATDALM TGFTGDFDSVIDCNTCVTQTVDFSLDPTFTIETITLPQDAVSRTQRRGRTGRGK PGIYRFVAPGERPSGMFDSSILCECYDAGCAWYELTPAETTVRLRAYMNTPGL PVCQDHLEFWEGVFTGLTHIDAHFLSQTKQSGENLPYLVAYQATVCARARAPP PSWDQMWKCLIRLKPTLHGATPLLYRLGAVQNEITLTHPITKYIMACMSADLEVA TSTWVLVGGVLAALAAYCLTTGSWIVGRIILSGKPAVIPDREVLYQEFDEMEEC ATHLPYIEQGMQLAEQFRQKALGLLQTATKQAEAAVPVVESKWRALEAFWAKH MWNFISGIQYLAGLSTLPGNPAIVSLMAFTASVTSPLTTQHTLLFNILGGWVAAQ LAPPSAASAFVGAGIVGAAVGSVGLGKVLVDILAGYGAGVAGALVAFKVMSGD MPSTEDLVNLLPAILSPGALWGVVCAAVLRRHVGPGEGAVQWMNRLIAFASR GNHVSPTHYVPESDAAARVTQILSSLTITQLLKRLHRWINEDCSTPCSGSWLRD VWDWICTVLTDFKTWLQSKLMPRLPGVPFLSCQRGYKGIWRGDGIMHTTCPC GAQITGHVKNGSMRIVGPKTCSNTWHGTFPINAYTTGPCTPLPAPNYKFALWR VSAEEYVEIRRVGDFHYVTGMTTDNIKCPCQVPAPEFFTELDGVRLHRYAPACK PLLRDEVTFQVGLNQYWGSQLPCEPEPDVTVLTSMLTDPSHITAETAKRRLAR GSPPSMASSSASQLSAPSLKATCTTHHDSPDADLIEANLLWRQEMGGNITRVE SENKWVLDSFDPLRAEEDEREVSVPAEILRKSRKFPRAMPIWARPDYNPPLIE SWKDPDYAPPWHGCPLPPTKAPPIPPPRRKRTVVLSESTVSSALAELATKTFG SSGSSAVDSGTATAPPDQASDDGDKGSDVESYSSMPPLEGEPGDPDLNDGS WSTVSEEASEDWCCSMSYSWTGALITPCVAEESKLPINALSNSLLRHHNMVY ATTSRSASQRQKKVTFDRLQVLDNHYQDVLKEMKAKASTVKAKLLSVEEACKL TPPHSARSKFGYGAKDVRNLSSKAVNHIRSVWKDLLEDTETPIDTTVMAKNEVF CVQPEKGGRKPARLIVYPDLGVRVCEKMALYDWSTLPQAVMGSSYGFQYSP GQRVEFLVNAWKSKKNPMGFAYDTRCFDSTVTENDIRVEESIYQSCDLAPEAR QAIRSLTERLYIGGPLTNSKGQSCGYRRCRASGVLTTSCGNTLTCYLKASAACR AAKLRDCTMLVCGDDLWICESAGTQEDAASLRVFTEAMTRYSAPPGDPPKPE YDLELITSCSSNVSVAHDATGKRVYYLTRDPATPFARAAWETARHTPVNSWLG NIIMFAPTLWVRMILMTHFFSILLAQEQLEKALDCQIYGATYSIEPLDLPQIIQRLH GLSAFSLHSYSPGEINRVASCLRKLGVPPLRVWRHRARSVRAKLLSQGGRAAT CGKYLFNWAVRTKLKLTPIPAASRLDLSGWFVAGYGGGDIYHSVSRARPRWFM WCLLLLSVGVGIYLLPNR

Design27.mosaic3 Amino Acid Sequence SEQ ID NO: 37 MSTNPKPQRRTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPKLGVRATR KTSERSQPRGRRQPIPKARRPEGRAWAQPGYPWPLYGNEGCGWAGWLLSP RGSRPSWGPNDPRRRSRNLGKVIDTLTCGLADLMGYIPLVGAPLGGAARA LAHGVRVLEDGVNYATGNIPGCSFSIFLLALLSCLTVPASAYQVRNSTGL YHVTNDCPNSSIVYEAADAILHTPGCVPCVREGNASRCWVAMTPTVATRD GKLPTTQLRRHIDLLVGSATLCSALYVGDLCGSVFLVGQLFTFSPRRHWT TQDCNCSIYPGHITGHRMAWDMMMNWSPTTALVVAQLLRIPQAILDMIAG AHWGVLAGIAYFSMVGNWAKVLVVLLLFAGVDAGTHVTGGSAAKDTSGFT SLFRIGARQNIQLINTNGSWHINRTALNCNASLDTGWVAGLFYYHKFNSS GCPERLASCRPLADFDQGWGPISYANGSGPEHRPYCWHYPPKPCGIVPAK SVCGPVYCFTPSPVVVGTTDRFGAPTYNWGENETDVLILNNTRPPQGNWF GCTWMNGTGFTKTCGAPPCNIGGVGNNTLTCPTDCFRKHPEATYTKCGSG PWLTPRCLVDYPYRLWHYPCTVNFTIFKVRMYVGGVEHRLEAACNWTRGE RCNLEDRDRSELSPLLLSTTEWQVLPCSFTTLPALSTGLIHLHRNIVDVQ YLYGIGSAVVSFAIKWEYVLLLFLLLADARVCACLWMMLLIAQAEAALEN LVVLNAASVAGAHGILSFLVFFCAAWYIKGKLVPGAAYAFYGVWPLLLLL LALPPRAYAMDREVAASCGGAVFIGLALLTLSPHYKAFLAKLIWWLQYLI TRAEAHLQVWVPPLNVRGGRDAIILLTCAVHPELIFDITKLLLAILGPLM VLQAGLTRVPYFVRAQGLIRMCMLVRKAAGGHYVQMALMKLAALTGTYVY DHLTPLQDWAHAGLRDLAVAVEPVIFSDMETKVITWGADTAACGDIILGL PVSARRGREILLGPADSLEGQGWRLLAPITAYSQQTRGLLGCIITSLTGR DRNQVEGEVQVVSTATQSFLATCINGVCWTVFHGAGSKTLAGPKGPVTQM YTNVDQDLVGWQAPPGARSLTPCTCGSSDLYLVTRHADVIPVRRRGDNRG SLLSPRPISYLKGSSGGPLLCPSGHAVGIFRAAVCTRGVAKAVDFVPVES METTMRSPVYTDNSSPPAVPQTFQVAHLHAPTGSGKSTRVPAAYAAQGYK VLVLNPSVAATLSFGAYMSKAHGVDPNIRTGVRTITTGAPITYSTYGKFL ADGGCSGGAYDIIMCDECHSTDSTSILGIGTVLDQAETAGARLTVLATAT PPGSVTVPHPNIEEVALSNIGEIPFYGKAIPIETIKGGRHLIFCHSKKKC DELAAKLSGLGLNAVAYYRGLDVSVIPTSGNVVVVATDALMTGYTGDFDS VIDCNTCVTQSVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGRRGIYR FVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETSVRLRAYLNTPGLPV CQVHLEFWESVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARAQAP PPSWDQMWKCLTRLKPTLHGPTPLLYRLGPVQNEVTLTHPITKFIMACMS ADLEVVTSTWVLVGGVLAALAAYCLSTGCVVIVGRIVLSGKPAIIPDREV LYREFDEMEECSQHLPYIEQGMMLAEQFKQKALGLLQTASRQAEVIAPAV QTNWQKLEAFWAKHMWNFISGVQYLAGLSTLPGNPPIASLMAFTASITSP LTTQSTLLFNILGGWLAAQLAPPSAASAFVGAGIAGAAVGSIGLGKVLVD VLAGYGAGVAGALVAFKVMSGEMPSTEDLVNLLPAILSPGALVVGVVCAA ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVQESDAAARVTAILSS LTVTQLLRRLHQWISSECTTPCSGSWLRDIWDWICEVLSDFKTWLKAKLM PQLPGIPFVSCQRGYRGVWRGDGIMHTRCHCGAEITGHVKNGTMRIVGPR TCRNMWSGTFPINAYTTGPSTPLPAPNYTFALWRVSAEEYVEIRQVGDFH YVTGMTTDNLKCPCQVPSPEFFTELDGVRLHRFAPPCKPLLREEVSFRVG LHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAGRRLARGSPPSVAS SSASQLSAPSLKATCTANHDSPDAELIEANLLWRQEMGSNITRVESENKV VILDSFDPLVAEEDEREISVPAEILRKSRRFAQALPVWARPDYNPPLLET WKKPDYEPPVVHGCPLPPPQSPPVPPPRKKRTVVLTESTVSTALAELATK SFGSSSTSGITGDNTTTSSEPAPSGCPPDSDAESYSSMPPLEGEPGDPDF SDGSWSTVSSGADTEDVVCCSMSYSWTGALVTPCAAEEQKLPINALSNSL LRHHNLVYSTTSRSACQRQKKVTFDRLQVLDSHYQDVLKEVKAAASKVKA NLLSVEEACSLTPPHSARSKYGYGAKDVRCHARKAVNHINSVWKDLLEDS VTPIDTTIMAKNEVFCIQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVS KLPLAVMGSSYGFQYSPGQRVEFLVQAWKSKKTPMGFSYDTRCFDSTVTE SDIRTEEAIYQCCDLDPQARVAIKSLTERLYVGGPLTNSRGENCGYRRCR ASGVLTTSCGNTLTCYIKARAACRAAGLQDCTMLVCGDDLVVICESAGVQ EDAASLRAFTEAMTRYSAPPGDPPQPEYDLELITSCSSNVSVAHDGAGKR VYYLTRDPTTPLARAAWETARHTPINSWLGNIIMFAPTLWARMILMTHFF SVLIARDQLEQALDCEIYGACYSIEPLDLPPIIQRLHGLSAFSLHSYSPG EINRVASCLRKLGVPPLRAWRHRARNVRARLLSRGGRAAICGRYLFNWAV RTKLKLTPIAAAGQLDLSGWFTAGYSGGDIYHSVSHARPRWFWFCLLLLA AGVGIYLLPNR

Design28.mosaic1 Amino Acid Sequence SEQ ID NO: 38 MSTNPKPQRRTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPKLGVRATR KTSERSQPRGRRQPIPKARRPEGRAWAQPGYPWPLYGNEGLGWAGWLLSP RGSRPSWGPNDPRRRSRNLGKVIDTLTCGFADLMGYIPFVGAPLGGAARA LAHGVRALEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSTGL YHVTNDCPNSSIVYEAADAILHTPGCVPCVRENNSSRCWVALTPTLAARN ASVPTTTIRRHVDLLVGTAAFCSAMYVGDLCGSVLLVSQLFTFSPRRHET VQDCNCSIYPGHVTGHRMAWDMMMNWSPTTALVVSQLLRIPQAVMDMVAG AHWGVLAGLAYYSMAGNWAKVLIVMLLFAGVDGGTYVTGGTMAKNTLGIT SLFSPGSSQKIQLVNTNGSWHINRTALNCNDSLNTGFLAALFYTHKFNAS GCPERMASCRSIDKFDQGWGPITYAEPHDLDQRPYCWHYAPRPCGIVPAS EVCGPVYCFTPSPVVVGTTDRFGVPTYSWGENETDVLLLNNTRPPQGNWF GCTWMNGTGFTKTCGGPPCNIGGVGNNTLICPTDCFRKHPEATYTKCGSG PWLTPRCLVHYPYRLWHYPCTVNFTIFKVRMYVGGVEHRLEAACNWTRGE RCNLEDRDRSELSPLLLSTTEWQVLPCSFTTLPALSTGLIHLHQNVVDVQ YLYGIGSAVVSFAIKWEYVLLLFLLLADARVCACLWMMLLIAQAEAALEN LVVLNAASVAGAHGILSFLVFFCAAWYIKGKLVPGAAYAFYGVWPLLLLL MALPARAYAMDREMAASCGGAVFVGLVLLTLSPYYKVFLAKLIWWLQYLI TRAEAHLQVWIPPLNVRGGRDAIILLTCAIHPELIFTITKILLAILGPLM VLQAGITKVPYFVRAHGLIRACMLVRKAAGGHYVQMALMKLAALTGTYVY DHLTPLRDWAHAGLRDLAVAVEPVVFSDMETKVITWGADTAACGDIILGL PVSARRGKEIFLGPADSLEGQGWRLLAPITAYSQQTRGLLGCIITSLTGR DRNQVEGEVQVVSTATQSFLATCINGVCWTVFHGAGSKTLAGPKGPVTQM YTNVDQDLVGWQAPPGARSLTPCTCGSSDLYLVTRHADVIPVRRRGDNRG SLLSPRPISYLKGSSGGPLLCPSGHAVGIFRAAVCTRGVAKAVDFVPVES METTMRSPVFTDNSSPPAVPQTFQVAHLHAPTGSGKSTKVPAAYASQGYK VLVLNPSVAATLSFGAYMSKAHGVDPNIRTGIRTITTGAPITYSTYGKFL ADGGCSGGAYDIIICDECHSTDSTTILGIGTVLDQAETAGVRLTVLATAT PPGSVTVPHPNIEEVALSNIGEIPFYGKAIPIETIKGGRHLIFCHSRKKC DELAAKLSGLGLNAVAYYRGLDVSVIPTSGNVVVVATDALMTGFTGDFDS VIDCNTCVTQTVDFSLDPTFTIDTTTVPQDAVSRTQRRGRTGRGRRGIYR FVTPGERPSGMFDSSVLCECYDAGCAWYELTPSETTVRLRAYMNTPGLPV CQDHLEFWEGVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARSQAP PPSWDQMWKCLLRLKPTLHGATPLLYRLGAVQNEVTLTHPVTKYIMTCMS ADLEVVTSTWVLVGGVLAALAAYCLSTGCVVIVGRVVLSGKPAIVPDREV LYQEFDEMEECSQHLPYIEQGMALAEQFKQKALGLLQTASRQAEVITPAV QTNWQKLEVFWAKHMWNFISGIQYLAGLSTLPGNPPIASLMAFTASITSP LTTQNTLLFNILGGWVAAQLAAPGAATAFVGAGLAGAAVGSVGLGKVLVD IIAGYGAGVAGALVAFKIMSGEVPSTEDLVNLLPAILSPGALVVGVVCAA ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTAILSS LTVTQLLRRLHQWISSECTTPCSGSWLRDIWDWICEVLSDFKTWLKAKLM PQLPGIPFVSCQRGYKGVWRGDGVMHTRCHCGAEITGHVKNGTMRIVGPR TCRNMWSGTFPINAYTTGPCTPLPAPNYKFALWRVSAEEYVEIRQVGDFH YVTGMTTDNLKCPCQIPSPEFFTELDGVRLHRYAPPCKPLLREEVSFRVG LHDYPVGSQLPCEPEPDVTVVTSMLTDPSHITAEAAGRRLARGSPPSVAS SSASQLSAPSLKATCTTNHDSPDAELIEASLLWRQEMGGNITRVESENKI VILDSFEPLRAEEDEREVSVAAEILRKTRKFPAAMPVWARPDYNPPLIES WKDPDYVPPVVHGCPLPPTKAPPIPPPRRKRTVVLTESTVSSALAELATK TFGSSGSSAVDSGTATGPPDQASAEGDAGSDAESYSSMPPLEGEPGDPDF SDGSWSTVSEEASEDVVCCSMSYTWTGALITPCAAEETKLPINALSNSLL RHHNLVYATTSRSASLRQKKVTFDRMQVLDDHYRDVLKEMKAKASTVKAK LLSVEEACKLTPPHSARSKFGYGAKDVRNLSSKAVNHIHSVWKDLLEDTE TPIDTTIMAKNEVFCIQPEKGGRKPARLIVYPDLGVRVCEKMALYDVVST LPQAVMGSSYGFQYSPKQRVEFLVNAWKSKKCPMGFAYDTRCFDSTVTEN DIRVEESIYQCCDLAPEARQVIRSLTERLYIGGPLTNSKGENCGYRRCRA SGVLTTSCGNTLTCYIKAQAACRAAGLRDCTMLVCGDDLVVICESAGTQE DAANLRVFTEAMTRYSAPPGDLPQPEYDLELITSCSSNVSVAHDASGKRV YYLTRDPTTPLARAAWETVRHTPVNSWLGNIIMFAPTLWARMILMTHFFS VLIARDQLEQALDCEIYGACYSIEPLDLPPIIQRLHGLSAFSLHSYSPGE INRVATCLRKLGVPPLRAWRHRARNVRARLLSRGGRAAICGKYLFNWAVR TKLKLTPIAAAGRLDLSGWFTAGYSGGDIYHSVSHARPRWFWFCLLLLAA GVGIYLLPNR

Design28.mosaic2 Amino Acid Sequence SEQ ID NO: 39 MSTNPKPQRKIKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRVGVRATR KTSERSQPRGRRQPIPKARRPEGRSWAQPGYPWPLYGNEGCGWAGWLLSP RGSRPSWGPSDPRRRSRNLGKVIDTLTCGLADLMGYIPLVGAPLGGAARV LAHGVRVLEDGVNYATGNLPGCPFSIFLLALLSCLTIPASAYQVRNSSGL YHVTNDCPNSSIVYETADTILHSPGCVPCVREGNASRCWVAMTPTVATRD GKLPTTQLRRHIDLLVGSATLCSALYVGDLCGSVFLVGQLFTFSPRRHWT TQGCNCSIYPGHITGHRMAWDMMMNWSPTAALVMAQLLRIPQAILDMIAG AHWGVLAGMAYFSMVGNWAKVLVVLLLFAGVDAETHVTGGSAAKDTSGFT SLFRIGARQNIQLINSNGSWHINRTALNCNASLDTGWVAGLFYYHKFNSS GCPERMASCRPLADFDQGWGPISYANGSGPEHRPYCWHYPPKPCGIVPAQ NVCGPVYCFTPSPVVVGTTDKSGAPTYNWGANDTDVFVLNNTRPPLGNWF GCTWMNSSGFTKVCGAPPCVIGGVGNNTLHCPTDCFRKHPDATYSRCGSG PWITPRCLVNYPYRLWHYPCTVNYTLFKVRMYVGGVEHRLEVACNWTRGE RCDLDDRDRSELSPLLLSTTQWQILPCSFTTLPALTTGLIHLHQNTVDVQ YLYGVGSSIVSWAIKWEYVILLFLLLADARICSCLWMMLLISQAEAALEN LVLLNAASLAGTHGLASFLVFFCFAWYLKGKWVPGAAYAFYGMWPLLLLL LALPQRAYALDTEMAASCGGVVLVGLVALTLSPYYKRYISWCLWWLQYFL TRVEAHLHVWVPPLNARGGRDAVILLMCVVHPALVFDITKLLLAVFGPLW ILQTSLLKVPYFVRVQGLLRLCALARKMAGGHYVQMVIIKLGALTGTYIY NHLTPLRDWAHNGLRDLAVAVEPVVFSQMETKLITWGADTAACGDIINNL PVSARRGQEILLGPADGMVSKGWRLLAPITAYSQQTRGLLGCIVTSLTGR DKNQVEGEVQIVSTAAQTFLATCINGVCWTVYHGAGTRTIASSKGPVIQM YTNVDQDLVGWPAPQGARSLTPCACGSSDLYLVTRHADVIPVRRRGDGRG SLLSPRPISYLKGSSGGPLLCPAGHAVGIFRAAVCTRGVAKAVDFIPVES LETTMRSPVFTDNSTPPAVPQSYQVAHLHAPTGSGKSTRVPAAYAAQGYK VLVLNPSVAATLGFGVYMSKAHGIDPNIRTGVRTITTGAPVTYSTYGKFL ADGGCSGGAYDIIMCDECHSTDATSILGIGTALDQAETAGARLTVLATAT PPGSVTVSHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHLIFCHSKRKC DELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVSTDALMTGFTGDFDS VIDCNTCVIQTVDFSLDPTFTIETITLPQDAVSRTQRRGRTGRGKPGIYR FVAPGERPSGMFDSVVLCECYDAGCAWYELTPAETSVRLRAYLNTPGLPV CQDHLEFWEGVFTGLTRIDAHFLSQTKQSGENFPYLVAYQATVCARAQAP PPSWDQMWKCLTRLKPTLHGPTPLLYRLGAVQNEITLTHPITKYIMTCMA ADLEVVTSTWVLVGGVLAALTAYCLSTGCVVIVGRIVLSGKPAIIPDREV LYKEFDEMEECASHLPYIEQGMMLAEQFKQKALGLLQTASRQAEVIAPAV QTNWQKLEAFWAKHMWNFISGVQYLAGLSTLPGNPAIASLMAFTAAVTSP LTTSQTLLFNILGGWLAAQLAAPGAATTFVGAGLAGAAIGSVGLGKVLVD ILAGYGAGVAGALVAFKIMSGEAPSTEDLINLLPAILSPGALVVGIVCAA ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTTILSS LTVTQLLRRLHQWISSDCTTPCSGSWLRDVWDWICEVLSDFKTWLKAKLV PQLPGIPFVSCQRGYRGVWRGDGIMHTRCHCGAEIAGHVKNGTMRIVGPK TCRNMWSGTFPINAYTTGPCTPLPAPNYTFALWRVSAEEYVEIRRVGDFH YVTGMTADNLKCPCQVPSPEFFTEVDGVRLHRYAPACKPLLREEVTFQVG LNQYLVGSQLPCEPELDVTVLTSMLTDPSHITAEAAKRRLARGSPPSEAS SSASQLSAPSLKATCTTHHDSPDADLIEANLLWRQEMGGNITRVESENKV VILDSFEPLQAEEDEREVSVAAEILRKSRKFPPALPIWARPDYNPPLLES WKDPDYVPPVVHGCPLPPPRSPPVPPPRKKRTVVLTESTVSTALAELATK TFGSSGSSAADSGTATAPPDQASDDGDKGSDVESYSSMPPLEGEPGDPDL SDGSWSTVSSEAGTEDVVCCSMSYTWTGALITPCVAEESKLPINPLSNSL LRHHNMIYATTSRSAGLRQKKVTFDRLQVLDDHYRDVLMEVKAKASTVKA KLLSIEEACKLTPPHSAKSKFGYGAKDVRSLSSRAVNHIRSVWEDLLEDT ETPIDTTIMAKSEVFCVQPEKGGRKPARFIVFPDLGVRVCEKMALYDVVS TLPQAVMGPSYGFQYSPGQRVEFLVNTWKSKKCPMGFSYDTRCFDSTVTE NDIRTEESIYQCCDLAPEARQAIRSLTERLYVGGPLTNSKGQNCGYRRCR ASGVLTTSCGNTLTCYLKATAACRAAKLQDCTMLVNGDDLVVICESQGVQ EDAANLRAFTEAMTRYSAPPGDPPQPEYDLELITSCSSNVSVAHDGAGKR VYYLTRDPETPLARAAWETARHTPINSWLGNIIMFAPTLWVRMILMTHFF SILLAQEQLEKALGCQIYGATYFIEPLDLPQIIERLHGLSAFTLHSYSPG EINRVASCLRKLGVPPLRAWRHRARSVRAKLLSRGGRAATCGKYLFNWAV KTKLKLTPIAAAGQLDLSGWFTAGYGGGDIYHSVSRARPRWFWFCLLLLT AGVGIYLLPNR

Design28.mosaic3 Amino Acid Sequence SEQ ID NO 40  MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRAPR KTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGMGWAGWLLSP RGSRPNWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGGPLGGAARA LAHGVRVLEDSVNYATGNLPGCSFSIFLLALLSCLTTPASAYEVRNVSGI YHVTNDCSNASIVYEAADLIMHTPGCVPCVRESNFSRCWVALTPTLAARN SSIPTTTIRRHVDLLVGAAALCSAMYVGDLCGSVFLVSQLFTFSPRRHWT TQDCNCSIYPGHVSGHRMAWDMMMNWSPTTALVVAQLLRIPQAIMDMIAG AHWGVLAGIAYFSMVGNWAKVMVVLLLFAGVDGHTHVTGGRVASSTQSLV SWLSQGPSQKIQLVNTNGSWHINRTALNCNDSLQTGFLAALFYTHRFNAS GCPERMASCRPIDKFAQGWGPITHVVPNISDQRPYCWHYAPQPCGIVPAS QVCGPVYCFTPSPVVVGTTDRFGAPTYNWGENETDVLILNNTRPPQGNWF GCTWMNSTGFTKTCGGPPCNIGGAGNNTLTCPTDCFRKHPEATYTRCGSG PWLTPRCLVDYPYRLWHYPCTVNFTVFKVRMYVGGVEHRLNAACNWTRGE RCDLEDRDRSELSPLLLSTTEWQILPCSFTTLPALSTGLIHLHRNIVDVQ YLYGVGSAVVSFAIKWEYILLLFLLLADARICACLWMMLLVAQAEAALEN LVVLNAASVAGTHGILSLLVFFCAAWYIKGRLVPGAAYALYGVWPLLLLL LALPPRAYAMDREMAASCGGAVFIGLALLTLSPHYKVFLARLIWWLQYFI TRAEAHLQVWVPPLNVRGGRDAIILLTCAVHPELIFDITKLLLAILGPLM VLQAGITRVPYFVRAQGLIRACMLVRKVAGGHYVQMAFMKLAALTGTYVY DHLTPLQDWAHTGLRDLAVAVEPVIFSDMETKIITWGADTAACGDIISGL PVSARRGKEILLGPADSFGEQGWRLLAPITAYSQQTRGLFGCIITSLTGR DKNQVDGEVQVLSTATQSFLATCVNGVCWTVYHGAGSKTLAGPKGPITQM YTNVDQDLVGWPAPPGARSMTPCTCGSSDLYLVTRHADVIPVRRRGDTRG SLLSPRPVSYLKGSSGGPLLCPSGHVVGIFRAAVCTRGVAKAVDFIPVES METTMRSPIFTDNSSPPAVPQCYQVAHLHAPTGSGKSTKVPAAYAAQGYK VLVLNPSVAATLGFGAYMSKAYGVDPNIRTGVRTITTGASITYSTYGKFL ADGGCSGGAYDIIMCDECHSTDSTSILGIGTVLDQAETAGARLVVLATAT PPGSITVPHPNIEEVALSNTGEIPFYGKAIPLEAIKGGRHLIFCHSKKKC DELAAKLVALGVNAVAYYRGLDVSIIPTSGDVVVVATDALMTGYTGDFDS VIDCNTCVTQSVDFSLDPTFTIETTTLPQDAVSRAQRRGRTGRGRMGIYR FVTPGERPSGMFDSSILCECYDAGCAWYELTPAETTVRLRAYLNTPGLPV CQVHLEFWESVFTGLTHIDAHFLSQTKQAGENFPYLTAYQATVCARALAP PPSWDQMWKCLIRLKPTLHGPTPLLYRLGAVQNEVILTHPITKYIMACMS ADLEIVTSTWVLVGGVLAALAAYCLTTGCVVIVGRIILSGRPAVIPDREV LYREFDEMEECASHLPYIEQGMQLAEQFKQKALGLLQTATKQAEAAAPAV ESKWRALETFWAKHMWNFISGIQYLAGLSTLPGNPAIASLMAFTASVTSP LTTQSTLLFNILGGWVAAQLAPPSAASAFVGAGIAGAAIGSIGLGKVLVD ILAGYGAGVAGALVAFKVMSGEMPSTEDLVNLLPAILSPGALVVGVVCAA VLRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQILSS LTITQLLKRLHRWINEDCSTPCSGSWLKDVWDWICTVLSDFKTWLQSKLL PRLPGVPFFSCQRGYKGVWRGDGIMQTTCPCGAQITGHVKNGSMRIVGPR TCSNTWHGTFPINAHTTGPCTPSPAPNYSRALWRVAAEEYVEVTRVGDFH YVTGMTTDNVKCPCQVPAPEFFTELDGVRLHRFAPPCKPLLRDEVSFRVG LHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAARRRLARGSPPSMAS SSASQLSAPSLKATCTANHDSPDAELIEANLLWRQEMGSNITRVESENKV VVLDSFDPLVAEEDEREISVPAEILRKSRRFAQALPVWARPDYNPPLLET WKKPDYEPPVVHGCPLPPPQSPPVPPPRKKRTVVLTESTLSTALAELATK SFGSSSTSGITGDNTTTSSEPAPSGCPPDSDAESCSSMPPLEGEPGDPDL SDGSWSTVSSGADTEDVVCCSMSYSWTGALVTPCAAEEQKLPINALSNSL LRHHNLVYSTTSRSACQRQKKVTFDRLQVLDSHYQDVLKEVKAAASKVKA NLLSVEEACSLTPPHSAKSKFGYGAKDVRCHARKAVNHINSVWKDLLEDS VTPIDTTIMAKNEIFCVQPEKGGRKAARLIVFPDLGVRVCEKMALYDVVS KLPLAVMGSSYGFQYSPGQRVEFLVQAWKSKKTPMGFSYDTRCFDSTVTE SDIRTEEAIYQCCDLDPQARVAIKSLTERLYVGGPLTNSRGENCGYRRCR VSGVLTTSCGNTLTCYIKARAACRAAGLQDCTMLVCGDDLVVICESAGVQ EDAASLRAFTEAMTRYSAPPGDPPKPEYDLELITSCSSNVSVAHDDAGKR VYYLTRDPAIPLARAAWETVRHTPVNSWLGNIIMYAPTLWARMVLMTHFF SILIAQEQLEKALDCQIYGACYSIEPLDLPLIIQRLHGLSAFSLHSYSPG EINRVASCLRKLGVPPLRTWRHRARSVRARLLSQGGRAATCGRYLFNWAV RTKLKLTPIPAASQLDLSGWFVAGYNGGDIYHSLSRARPRWFMLCLLLLS VGVGIYLLPNR

Design28.mosaic4 Amino Acid Sequence SEQ ID NO: 41 MSTNPKPQRQTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATR KTSERPQPRGRRQPIPKARQPEGRAWAQPGYPWPLYANEGMGWAGWLLSP RGSRPSWGPTDPRRRSRNLGRVIDTLTCGFADLMGYIPLVGAPLGGVARA LAHGVRVVEDGVNYATGNLPGCSFSIFLLALLSCLTIPASAYEVRNVSGV YHVTNDCSNSSIVYEAADMIMHTPGCVPCVREGNSSRCWVALTPTLAARN ASIPTTTIRRHVDLLVGAAAFCSAMYVGDLCGSVFLISQLFTFSPRRYET VQDCNCSLYPGHVSGHRMAWDMMMNWSPTAALVVSQLLRIPQAVVDMVAG AHWGILAGLAYYSMVGNWAKVLIVLLLFAGVDGNTRVSGGEAAKNTMGFA SLFVSGPSQKIQLINTNGSWHINSTALNCNESLNTGWLAGLFYHNKFNSS GCPERLASCRPLTDFAQGWGPISHANGSGPDQRPYCWHYPPRPCGIVPAK SVCGPVYCFTPSPVVVGTTDRSGAPTYTWGENETDVFVLNNTRPPMGNWF GCTWMNSTGFTKVCGAPPCAIGGVGNNTLRCPTDCFRKHPEATYSRCGSG PWITPRCMVDYPYRLWHYPCTINYTIFKVRMYVGGVEHRLDAACNWTRGE RCNLDDRDRSELSPLLLSTTQWQVLPCSFTPMPALSTGLIHLHQNIVDVQ YLYGVGSSIASWAIKWEYVVLLFLLLADARVCSCLWMMLLISQVEAALEN LVILNAASLAGTHGLVSFLVFFCFAWYLKGRWVPGAVYALYGMWPLLLLL LALPQRAYALDTEVAASCGGVVLVGLMALTLSPYYKHYISWCMWWLQYFL TRVEAQLHVWVPPLNVRGGRDAVILLTCVVHPTLVFDITKLLLAIFGPLW ILQASLLKVPYFVRVQGLLRICALARKMVGGHYVQMAIIKLGALTGTYVY NHLTPLRDWAHNGLQDLAVAVEPVVFSRMETKLITWGADTAACGDIINGL PVSARRGREILLGPADGMASKGWRLLAPITAYAQQTRGLLGCIVTSLTGR DKNQAEGEVQIVSTATQTFLATCINGVCWTVYHGAGTRTIASPKGPVIQM YTNVDKDLVGWPAPQGSRSLTPCTCGASDLYLVTRHADVIPVRRRGDSRG SLLSPRPISYLKGSSGGPLLCPAGHAVGLFRAAVCTRGVAKAVDFIPVEN LETTMRSPVFTDNSSPPAVPQSFQVAHLHAPTGSGKSTKVPAAYAAQGYT VLVLNPSVAATLAFGAYMSKAHGIDPNVRTGVRTITTGSPITYSTYGKFL ADGGCPGGAYDIIICDECHSTDATTILGVGTVLDQAETAGARLVVLATAT PPGSVTVPHSNIEEVALSNVGEIPFYGKAIPIEAIKGGRHLIFCHSKKKC DELAAKLSALGLNAVAYYRGLDVSVIPASGDVVVVATDALMTGYTGDFDS VIDCNTCVTQTVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGRGGIYR FVTPGERPSGMFDSSVLCESYDAGCAWYELTPAETSIRLRAYLNTPGLPV CQDHLEFWESVFTGLTHIDAHFLSQTKQSGENLPYLVAYQATVCARAQAL PPSWDQMWKCLVRLKPTLHGPTPLLYRLGPVQNEVTLTHPITKFIMACMS ADLEVVTSTVVVLVGGVLAALAAYCLTTGSVVIVGRIILSGKPAVIPDRE VLYQEFDEMEECATHLPYIEQGMQLAEQFKQKALGLLQTASKQAEAAAPV VESKWRALEAFWAKHMWNFISGIQYLAGLSTLPGNPAIVSLMAFTASITS PLTTQHTLLFNILGGWVAAQLAPPSAASAFVGAGIAGAAVGSIGLGKVLV DIIAGYGAGVAGALVAFKVMSGDMPSTEDLVNLLPAILSPGALVVGVVCA AVLRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQILS NLTITQLLKRLHQWINEDCSTPCSGTWLRDVWDWICTVLTDFKTWLQSKL LPRLPGVPFLSCQRGYKGVWRGDGIMHTTCPCGAQIAGHVKNGSMRIVGP KTCSNTWHGTFPINAYTTGPCTPSPAPNYSKALWRVAAEEYVEITRVGDF HYVTGMTTDNIKCPCQVPAPEFFTEVDGVRLHRYAPACKPLLRDEVTFQV GLNQYVVGSQLPCEPEPDVTVLTSMLTDPSHITAETAKRRLARGSPPSLA SSSASQLSAPSLKATCTTRHDSPDADLIEANLLWRQAMGGNITRVESENK VVILDSFDPLRAEEDEREVSVPAEILRRSRKFPPAMPIWARPDYNPPLVE PWKRPDYEPPLVHGCPLPPAKAPPVPPPRRKRTVVLSESTVSSALAELAT KTFGSSESSAVDSGTATAPPDQPSDDGDAGSDVESYSSMPPLEGEPGDPD LSDGSWSTVSEEAGEDVVCCSMSYSWTGALITPCAAEESKLPINALSNSL LRHHNMVYATTSRSASQRQKKVTFDRLQVLDNHYQDVLKEMKAKASTVKA RLLSVEEACSLTPPHSARSKFGYGAKDVRNLSGKAVNHIRSVWKDLLEDT DTPIDTTIMAKNEVFCVQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVS KLPVAVMGSSYGFQYSPGQRVEFLVNAWKSKKNPMGFAYDTRCFDSTVTE SDIRVEESIYQCCDLAPEARQAIKSLTERLYIGGPLTNSKGQSCGYRRCR ASGVLTTNCGNTLTCYLKASAACRAAKLRDCTMLVCGDDLVVICESAGTQ EDAASLRVFTEAMTRYSAPPGDPPRPEYDLELITSCSSNVSVAHDATGKR VYYLTRDPTTPIARAAWETARHTPVNSWLGNIIMYAPTLWVRMILMTHFF SILLAQEQLGKALDCQIYGATYSIEPLDLPQIIQRLHGLSAFSLHSYSPG EINRVAACLRKLGVPPLRVWRHRARSVRAKLLSQGGRAAICGRYLFNWAV KTKLKLTPIPAASRLDLSGWFVAGYSGGDIYHSLSRARPRWFMWCLLLLS VGVGIYLLPNR

Design29.mosaic1_serial Amino Acid Sequence SEQ ID NO: 42 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATR KTSERSQPRGRRQPIPKARQPEGRAWAQPGYPWPLYGNEGMGWAGWLLSP RGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARA LAHGVRVLEDGVNYATGNLPGCSFSIFLLALLSCLTIPASAYEVRNVSGV YHVTNDCSNSSIVYEAADMIMHTPGCVPCVRENNSSRCWVALTPTLAARN ASVPTTTIRRHVDLLVGAAAFCSAMYVGDLCGSVFLVSQLFTFSPRRHET VQDCNCSIYPGHVSGHRMAWDMMMNWSPTTALVVSQLLRIPQAVVDMVAG AHWGVLAGLAYYSMVGNWAKVLIVMLLFAGVDGHTHVTGGRVASSTQSLV SWLSQGPSQKIQLVNTNGSWHINRTALNCNDSLQTGFLAALFYTHKFNAS GCPERMASCRPIDEFAQGWGPITHDMPESSDQRPYCWHYAPRPCGIVPAS QVCGPVYCFTPSPVVVGTTDRFGVPTYSWGENETDVLLLNNTRPPQGNWF GCTWMNSTGFTKTCGGPPCNIGGVGNNTLTCPTDCFRKHPEATYTKCGSG PWLTPRCLVDYPYRLWHYPCTVNFTIFKVRMYVGGVEHRLNAACNWTRGE RCDLEDRDRSELSPLLLSTTEWQILPCSFTTLPALSTGLIHLHQNIVDVQ YLYGIGSAVVSFAIKWEYVLLLFLLLADARVCACLWMMLLIAQAEAALEN LVVLNAASVAGAHGILSFLVFFCAAWYIKGRLVPGAAYALYGVWPLLLLL LALPPRAYAMDREMAASCGGAVFVGLALLTLSPHYKVFLARLIWWLQYFI TRAEAHLQVWIPPLNVRGGRDAIILLTCAVHPELIFDITKLLLAILGPLM VLQAGITRVPYFVRAQGLIRACMLVRKVAGGHYVQMAFMKLAALTGTYVY DHLTPLRDWAHAGLRDLAVAVEPVVFSDMETKIITWGADTAACGDIILGL PVSARRGREILLGPADSLEGQGWRLLAPITAYSQQTRGLLGCIITSLTGR DKNQVEGEVQVVSTATQSFLATCVNGVCWTVYHGAGSKTLAGPKGPITQM YTNVDQDLVGWQAPPGARSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRG SLLSPRPVSYLKGSSGGPLLCPSGHAVGIFRAAVCTRGVAKAVDFVPVES METTMRSPVFTDNSSPPAVPQTFQVAHLHAPTGSGKSTKVPAAYAAQGYK VLVLNPSVAATLGFGAYMSKAHGVDPNIRTGVRTITTGAPITYSTYGKFL ADGGCSGGAYDIIICDECHSTDSTTILGIGTVLDQAETAGARLVVLATAT PPGSVTVPHPNIEEVALSNTGEIPFYGKAIPIETIKGGRHLIFCHSKKKC DELAAKLSGLGLNAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDS VIDCNTCVTQTVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGRRGIYR FVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETSVRLRAYLNTPGLPV CQDHLEFWESVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARAQAP PPSWDQMWKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMACMS ADLEVVTSTWVLVGGVLAALAAYCLTTGSVVIVGRIILSGKPAIIPDREV LYQEFDEMEECASHLPYIEQGMQLAEQFKQKALGLLQTATKQAEAAAPVV ESKWRALETFWAKHMWNFISGIQYLAGLSTLPGNPAIASLMAFTASITSP LTTQHTLLFNILGGWVAAQLAPPSAASAFVGAGIAGAAVGSIGLGKVLVD ILAGYGAGVAGALVAFKVMSGEMPSTEDLVNLLPAILSPGALVVGVVCAA ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQILSS LTITQLLKRLHQWINEDCSTPCSGSWLRDVWDWICTVLTDFKTWLQSKLL PRLPGVPFFSCQRGYKGVWRGDGIMQTTCPCGAQITGHVKNGSMRIVGPK TCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAAEEYVEVTRVGDFH YVTGMTTDNVKCPCQVPAPEFFTEVDGVRLHRYAPACKPLLREEVTFQVG LNQYLVGSQLPCEPEPDVAVLTSMLTDPSHITAETAKRRLARGSPPSLAS SSASQLSAPSLKATCTTHHDSPDADLIEANLLWRQEMGGNITRVESENKV VILDSFDPLRAEEDEREVSVPAEILRKSRKFPRAMPIWARPDYNPPLLES WKDPDYVPPVVHGCPLPPTKAPPIPPPRRKRTVVLTESTVSSALAELATK TFGSSESSAVDSGTATAPPDQPSDDGDAGSDVESYSSMPPLEGEPGDPDL SDGSWSTVSEEASEDVVCCSMSYTWTGALITPCAAEESKLPINALSNSLL RHHNMVYATTSRSASQRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKAK LLSVEEACKLTPPHSARSKFGYGAKDVRNLSSKAVNHIRSVWKDLLEDTE TPIDTTIMAKNEVFCVQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVST LPQAVMGSSYGFQYSPGQRVEFLVNAWKSKKCPMGFAYDTRCFDSTVTEN DIRVEESIYQCCDLAPEARQAIRSLTERLYIGGPLTNSKGQNCGYRRCRA SGVLTTSCGNTLTCYLKASAACRAAKLQDCTMLVCGDDLVVICESAGTQE DAASLRVFTEAMTRYSAPPGDPPQPEYDLELITSCSSNVSVAHDASGKRV YYLTRDPTTPLARAAWETARHTPVNSWLGNIIMYAPTLWARMILMTHFFS ILLAQEQLEKALDCQIYGACYSIEPLDLPQIIQRLHGLSAFSLHSYSPGE INRVASCLRKLGVPPLRVWRHRARSVRAKLLSQGGRAATCGKYLFNWAVR TKLKLTPIPAASQLDLSGWFVAGYSGGDIYHSLSRARPRWFMWCLLLLSV GVGIYLLPNR

Design29.mosaic2_serial Amino Acid Sequence SEQ ID NO: 43 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRTTR KTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSP RGSRPNWGPTDPRRRSRNLGKVIDTLTCGLADLMGYIPLVGAPLGGAARA LAHGVRVLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSTGL YHVTNDCPNSSIVYEAADAILHTPGCVPCVREGNASRCWVAVTPTVATRD GKLPTTQLRRHIDLLVGSATLCSALYVGDLCGSVFLVGQLFTFSPRRHWT TQDCNCSIYPGHITGHRMAWDMMMNWSPTTALVVAQLLRIPQAILDMIAG AHWGVLAGIAYFSMVGNWAKVLVVLLLFAGVDAGTHVTGGSAAKDTSGFT SLFRIGARQNIQLINTNGSWHINSTALNCNASLDTGWIAGLFYYHKFNSS GCPERLASCRPLTDFDQGWGPISYANGSGPDQRPYCWHYPPKPCGIVPAK SVCGPVYCFTPSPVVVGTTDRSGAPTYSWGENDTDVFVLNNTRPPLGNWF GCTWMNSSGFTKVCGAPPCVIGGVGNNTLHCPTDCFRKHPEATYSRCGSG PWITPRCLVNYPYRLWHYPCTINYTIFKVRMYVGGVEHRLEAACNWTRGE RCDLDDRDRSELSPLLLSTTQWQVLPCSFTTLPALTTGLIHLHQNIVDVQ YLYGVGSSIASWAIKWEYVVLLFLLLADARVCSCLWMMLLISQAEAALEN LVILNAASLAGTHGLVSFLVFFCFAWYLKGRWVPGAVYALYGMWPLLLLL LALPQRAYALDTEVAASCGGVVLVGLMALTLSPYYKRYISWCLWWLQYFL TRVEAQLHVWVPPLNVRGGRDAVILLMCVVHPTLVFDITKLLLAVFGPLW ILQASLLKVPYFVRVQGLLRICALARKMAGGHYVQMAIIKLGALTGTYVY NHLTPLRDWAHNGLRDLAVAVEPVVFSQMETKLITWGADTAACGDIINGL PVSARRGQEILLGPADGMVSKGWRLLAPITAYAQQTRGLLGCIVTSLTGR DKNQVEGEVQIVSTAAQTFLATCINGVCWTVYHGAGTRTIASPKGPVIQM YTNVDKDLVGWPAPQGARSLTPCTCGSSDLYLVTRHADVIPVRRRGDGRG SLLSPRPISYLKGSSGGPLLCPAGHAVGIFRAAVCTRGVAKAVDFIPVEN LETTMRSPVFTDNSSPPAVPQSFQVAHLHAPTGSGKSTKVPAAYAAQGYT VLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTITTGSPITYSTYGKFL ADGGCSGGAYDIIICDECHSTDATSILGIGTVLDQAETAGARLTVLATAT PPGSITVPHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHLIFCHSKRKC DELAAKLVALGINAVAYYRGLDVSVIPASGDVVVVATDALMTGYTGDFDS VIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKPGIYR FVAPGERPSGMFDSSILCECYDAGCAWYELTPAETTVRLRAYMNTPGLPV CQDHLEFWEGVFTGLTHIDAHFLSQTKQSGENLPYLVAYQATVCARAQAL PPSWDQMWKCLTRLKPTLHGPTPLLYRLGAVQNEITLTHPVTKYIMTCMS ADLEVVTSTWVLVGGVLAALAAYCLSTGCVVIVGRIVLSGKPAIIPDREV LYREFDEMEECSQHLPYIEQGMMLAEQFKQKALGLLQTASRQAEVIAPAV QTNWQKLEAFWAKHMWNFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSP LTTSQTLLFNILGGWVAAQLAAPGAATAFVGAGLAGAAIGSVGLGKVLVD IIAGYGAGVAGALVAFKIMSGEVPSTEDLVNLLPAILSPGALVVGVVCAA ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVQESDAAARVTAILSS LTVTQLLRRLHQWISSECTTPCSGSWLRDIWDWICEVLSDFKTWLKAKLM PQLPGIPFVSCQRGYRGVWRGDGIMHTRCHCGAEITGHVKNGTMRIVGPR TCRNMWSGTFPINAYTTGPCTPLPAPNYTFALWRVSAEEYVEIRQVGDFH YVTGMTTDNLKCPCQVPSPEFFTELDGVRLHRFAPPCKPLLREEVSFRVG LHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAGRRLARGSPPSVAS SSASQLSAPSLKATCTANHDSPDAELIEANLLWRQEMGGNITRVESENKV VVLDSFDPLVAEEDEREISVPAEILRKSRRFAPALPIWARPDYNPPLLET WKKPDYEPPVVHGCPLPPPQSPPVPPPRKKRTVVLTESTVSTALAELATK SFGSSSTSGITGDNTTTSSEPAPSGCPPDSDAESYSSMPPLEGEPGDPDL SDGSWSTVSSGADTEDVVCCSMSYSWTGALVTPCAAEEQKLPINALSNSL LRHHNLVYSTTSRSACQRQKKVTFDRLQVLDSHYQDVLKEVKAAASKVKA NLLSVEEACSLTPPHSAKSKFGYGAKDVRCHARKAVNHINSVWKDLLEDS VTPIDTTIMAKNEVFCVQPEKGGRKPARLIVYPDLGVRVCEKMALYDVVS KLPLAVMGSSYGFQYSPGQRVEFLVQAWKSKKTPMGFSYDTRCFDSTVTE SDIRTEEAIYQCCDLDPQARVAIKSLTERLYVGGPLTNSRGENCGYRRCR ASGVLTTSCGNTLTCYIKARAACRAAGLQDCTMLVCGDDLVVICESAGVQ EDAASLRAFTEAMTRYSAPPGDPPQPEYDLELITSCSSNVSVAHDGAGKR VYYLTRDPTTPLARAAWETARHTPINSWLGNIIMFAPTLWARMILMTHFF SVLIARDQLEQALDCEIYGACYSIEPLDLPPIIQRLHGLSAFSLHSYSPG EINRVAACLRKLGVPPLRAWRHRARSVRARLLSRGGRAAICGKYLFNWAV KTKLKLTPIAAAGQLDLSGWFTAGYSGGDIYHSVSHARPRWFWFCLLLLA AGVGIYLLPNR

Design29.mosaic3_serial Amino Acid Sequence SEQ ID NO: 44 MSTNPKPQRKTKRNTNRRPQNVKFPGGGQIVGGVCLLPRRGPRVGVRATR KTSERSQPRGRRQPIPKARRPEGRSWAQPGYPWPLYGNEGCGWAGWLLSP RGSRPSRGPSDPRRRSRNLGKVIDTLTYGFADLMGYIPLVGAPLGGAARA LAHGVRVLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAVGVRNSSGV YHVTNDCPNASVVYETDSLIIHLPGCVPCVREGNGSRCWVSLSPTVAAKD PGVPVNEIRRHVDLIAGAAAFCSAMYVGHLCGSIFLVGQLFTLSPRRHWT TQDCNCSIYPGHVTGHRMAWDMMMNWSPTGALVVAQLLRIPQAVLDMIAG AHWGVLAGPAYYSMVGNWAKVVVVLLLFAGVDATTQVTGGTAGRNAYRLA SLFSTGPSQNIQLINSNGSWHINRTALNCNDSLHTGWVAALFYSHKFNSS GRPERMASCRPLTAFDQGWGPITHEGNASDDQRPYCWHYALRPCGIVPAK KVCGPVYCFTPSPVVVGTTDRAGVPTYRWGANETDVLLLNNSRPPMGNWF GCTWMNSSGFTKTCGAPACNVGGSETNTLSCPTDCFRRHPDATYAKCGSG PWLNPRCMVDYPYRLWHYPCTVNYTIFKIRMFVGGVEHRLDAACNWTRGE RCDLDDRDRAELSPLLLSTTQWQVLPCSFTTLPALSTGLIHLHQNIVDVQ YLYGLSSAVTSWVIKWEYVVLLFLLLADARICACLWMMLLISQVEAALEN LIVLNAASLVGTHGIVPFFIFFCAAWYLKGKWAPGLAYSVYGMWPLLLLL LALPQRAYALDQELAASCGATVFICLAVLTLSPYYKQYMARGIWWLQYML TRAEALLQVWVPPLNARGGRDGVVLLTCVLHPHLLFEITKIMLAILGPLW ILQASLLRVPYFVRAHGLIRLCMLVRKTAGGHYVQMALLKLGALTGTYIY NHLSPLQDWAHSGLRDLAVATEPVIFSRMEIKTITWGADTAACGDIINGL PVSARRGREVLLGPADALTDKGWRLLAPITAYAQQTRGLLGCIVTSLTGR DKNQVEGEIQIVSTATQTFLATCINGACWTVYHGAGSRTIASASGPVVRM YTNVDQDLVGWPAPQGARSLTPCTCGASDLYLVTRHADVIPVRRRGDNRG SLLSPRPISYLKGSSGGPLLCPMGHAVGIFRAAVCTRGVAKAVDFVPVES LETTMRSPVFTDNSSPPTVPQSYQVAHLHAPTGSGKSTKVPAAYAAQGYK VLVLNPSVAATLGFGAYMSKAHGIDPNVRTGVRTITTGSPITHSTYGKFL ADGGCPGGAYDIIICDECHSVDATSILGIGTVLDQAETAGVRLTVLATAT PPGLVTVPHSNIEEVALSADGEKPFYGKAIPLNYIKGGRHLIFCHSKKKC DELAAKLVGLGVNAVAFYRGLDVSVIPTTGDVVVVATDALMTGFTGDFDS VIDCNTCVVQTVDFSLDPIFSIETSTVPQDAVSRSQRRGRTGRGKHGIYR YVSPGERPSGMFDSVVLCECYDAGCAWYELTPAETTVRLRAYLNTPGLPV CQDHLEFWESVFTGLTHIDAHFLSQTKQSGENFPYLVAYQATVCARARAP PPSWDQMWKCLIRLKPTLTGATPLLYRLGSVQNEITLTHPITQYIMACMS ADLEVVTSTWVLVGGVLAALAAYCLSTGSVVIVGRIILGGKPAVIPDREV LYREFDEMEECAAHVPYLEQGMHLAEQFKQKALGLLQTASKQAETITPTV RTNWQKLESFWAKHMWNFVSGIQYLAGLSTLPGNPAIASLMSFTAAVTSP LTTQQTLLFNILGGWLAAQLAAPAAATAFVGAGITGAVVGSVGLGKVLVD ILAGYGAGVAGALVAFKIMSGETPTTEDLVNLLPAILSPGALVVAVVCAA ILRRHVGLGEGAVQWMNRLIAFASRGNHVSPTHYVPESDASARVTQILTS LTVTQLLKRLHVWISSDCIAPCASSWLKDVWDWICEVLSDFKNWLKAKLV PQLPGIPFVSCQRGYRGVWRGEGIVHTRCPCGANITGHVKNGSMRIVGPK TCSNTWRGSFPINAHTTGPCTPSPAPNYTFALWRVSAEEYVEVRRLGDFH YVTGVTTDKLKCPCQVPSPEFSTEVDGVRLHRYAPPCKPLLRDEVTFSIG LNEYLVGSQLPCEPEPDVAALTSMLTDPSHITAETAARRLKRGSPPSLAS SSASQLSAPSLKATCTTHHDSPDADLIEANLLWRREMGGNITRVESENKI VVLDSFDPLVAEEDDREISIPAEILRKFKQFPPAMPIWARPDYNPPLVEP WKRPDYEPPLVHGCPLPPPKPTPVPPPRRKRTVVLDESTVSSALAELATK TFGSSTTSGVTSGEAAESSPALSCDGELDSEAESYSSMPPLEGEPGDPDL SDGSWSTVSSDGGTEDVVCCSMSYSWTGALITPCAAEETKLPINALSNSL LRHHNLVYSTTSRSAGQRQKKVTFDRVQVLDDHYRDVLKEAKAKASTVKA RLLSVEEACSLTPPHSARSKFGYGPKDVRSHSSKAIRHINSVWQDLLEDN TTPIDTTIMAKNEVFCVKPEKGGRKPARLIVYPDLGVRVCEKRALYDVVK QLPIAVMGPSYGFQYSPAQRVDFLLNAWKSKKNPMGFSYDTRCFDSTVTE ADIRTEEDLYQSCDLVPEARAAIRSLTERLYIGGPLTNSKGQNCGYRRCR ASGVLTTSCGNTITCYLKASAACRAAKLRDCTMLVCGDDLVVICESAGVK EDAASLRAFTEAMTRYSGPPGDPAQPEYDLELITSCSSNVSVARDGAGKR VYYLTRDPETPLARAAWETARHTPVNSWLGNIIMFAPTLWVRMVLMTHFF SILIAQEHLEKALDCEIYGAVHSVQPLDLPEIIQRLHSLSAFSLHSYSPG EINRVAACLRKLGVPPLRAWRHRARSVRATLLSQGGKAAICGKYLFNWAV KTKLKLTPLPSMSQLDLSNWFTGGYSGGDIYHSVSHVRPRWFFWCLLLLS VGVGIYLLPNR

Design30.mosaic1_serial Amino Acid Sequence SEQ ID NO: 45 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATR KTSERSQPRGRRQPIPKARQPEGRAWAQPGYPWPLYGNEGMGWAGWLLSP RGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARA LAHGVRVLEDGVNYATGNLPGCSFSIFLLALLSCLTIPASAYEVRNVSGV YHVTNDCSNSSIVYEAADMIMHTPGCVPCVRENNSSRCWVALTPTLAARN ASVPTTTIRRHVDLLVGAAAFCSAMYVGDLCGSVFLVSQLFTFSPRRHET VQDCNCSIYPGHVSGHRMAWDMMMNWSPTTALVVSQLLRIPQAVVDMVAG AHWGVLAGLAYYSMVGNWAKVLIVMLLFAGVDGHTHVTGGRVASSTQSLV SWLSQGPSQKIQLVNTNGSWHINRTALNCNDSLQTGFLAALFYTHKFNAS GCPERMASCRPIDEFAQGWGPITHDMPESSDQRPYCWHYAPRPCGIVPAS QVCGPVYCFTPSPVVVGTTDRFGVPTYSWGENETDVLLLNNTRPPQGNWF GCTWMNSTGFTKTCGGPPCNIGGVGNNTLTCPTDCFRKHPEATYTKCGSG PWLTPRCLVDYPYRLWHYPCTVNFTIFKVRMYVGGVEHRLNAACNWTRGE RCDLEDRDRSELSPLLLSTTEWQILPCSFTTLPALSTGLIHLHQNIVDVQ YLYGIGSAVVSFAIKWEYVLLLFLLLADARVCACLWMMLLIAQAEAALEN LVVLNAASVAGAHGILSFLVFFCAAWYIKGRLVPGAAYALYGVWPLLLLL LALPPRAYAMDREMAASCGGAVFVGLALLTLSPHYKVFLARLIWWLQYFI TRAEAHLQVWIPPLNVRGGRDAIILLTCAVHPELIFDITKLLLAILGPLM VLQAGITRVPYFVRAQGLIRACMLVRKVAGGHYVQMAFMKLAALTGTYVY DHLTPLRDWAHAGLRDLAVAVEPVVFSDMETKIITWGADTAACGDIILGL PVSARRGREILLGPADSLEGQGWRLLAPITAYSQQTRGLLGCIITSLTGR DKNQVEGEVQVVSTATQSFLATCVNGVCWTVYHGAGSKTLAGPKGPITQM YTNVDQDLVGWQAPPGARSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRG SLLSPRPVSYLKGSSGGPLLCPSGHAVGIFRAAVCTRGVAKAVDFVPVES METTMRSPVFTDNSSPPAVPQTFQVAHLHAPTGSGKSTKVPAAYAAQGYK VLVLNPSVAATLGFGAYMSKAHGVDPNIRTGVRTITTGAPITYSTYGKFL ADGGCSGGAYDIIICDECHSTDSTTILGIGTVLDQAETAGARLVVLATAT PPGSVTVPHPNIEEVALSNTGEIPFYGKAIPIETIKGGRHLIFCHSKKKC DELAAKLSGLGLNAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDS VIDCNTCVTQTVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGRRGIYR FVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETSVRLRAYLNTPGLPV CQDHLEFWESVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARAQAP PPSWDQMWKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMACMS ADLEVVTSTWVLVGGVLAALAAYCLTTGSVVIVGRIILSGKPAIIPDREV LYQEFDEMEECASHLPYIEQGMQLAEQFKQKALGLLQTATKQAEAAAPVV ESKWRALETFWAKHMWNFISGIQYLAGLSTLPGNPAIASLMAFTASITSP LTTQHTLLFNILGGWVAAQLAPPSAASAFVGAGIAGAAVGSIGLGKVLVD ILAGYGAGVAGALVAFKVMSGEMPSTEDLVNLLPAILSPGALVVGVVCAA ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQILSS LTITQLLKRLHQWINEDCSTPCSGSWLRDVWDWICTVLTDFKTWLQSKLL PRLPGVPFFSCQRGYKGVWRGDGIMQTTCPCGAQITGHVKNGSMRIVGPK TCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAAEEYVEVTRVGDFH YVTGMTTDNVKCPCQVPAPEFFTEVDGVRLHRYAPACKPLLREEVTFQVG LNQYLVGSQLPCEPEPDVAVLTSMLTDPSHITAETAKRRLARGSPPSLAS SSASQLSAPSLKATCTTHHDSPDADLIEANLLWRQEMGGNITRVESENKV VILDSFDPLRAEEDEREVSVPAEILRKSRKFPRAMPIWARPDYNPPLLES WKDPDYVPPVVHGCPLPPTKAPPIPPPRRKRTVVLTESTVSSALAELATK TFGSSESSAVDSGTATAPPDQPSDDGDAGSDVESYSSMPPLEGEPGDPDL SDGSWSTVSEEASEDVVCCSMSYTWTGALITPCAAEESKLPINALSNSLL RHHNMVYATTSRSASQRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKAK LLSVEEACKLTPPHSARSKFGYGAKDVRNLSSKAVNHIRSVWKDLLEDTE TPIDTTIMAKNEVFCVQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVST LPQAVMGSSYGFQYSPGQRVEFLVNAWKSKKCPMGFAYDTRCFDSTVTEN DIRVEESIYQCCDLAPEARQAIRSLTERLYIGGPLTNSKGQNCGYRRCRA SGVLTTSCGNTLTCYLKASAACRAAKLQDCTMLVCGDDLVVICESAGTQE DAASLRVFTEAMTRYSAPPGDPPQPEYDLELITSCSSNVSVAHDASGKRV YYLTRDPTTPLARAAWETARHTPVNSWLGNIIMYAPTLWARMILMTHFFS ILLAQEQLEKALDCQIYGACYSIEPLDLPQIIQRLHGLSAFSLHSYSPGE INRVASCLRKLGVPPLRVWRHRARSVRAKLLSQGGRAATCGKYLFNWAVR TKLKLTPIPAASQLDLSGWFVAGYSGGDIYHSLSRARPRWFMWCLLLLSV GVGIYLLPNR

Design30.mosaic2_serial Amino Acid Sequence SEQ ID NO: 46 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRTTR KTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSP RGSRPNWGPTDPRRRSRNLGKVIDTLTCGLADLMGYIPLVGAPLGGAARA LAHGVRVLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSTGL YHVTNDCPNSSIVYEAADAILHTPGCVPCVREGNASRCWVAVTPTVATRD GKLPTTQLRRHIDLLVGSATLCSALYVGDLCGSVFLVGQLFTFSPRRHWT TQDCNCSIYPGHITGHRMAWDMMMNWSPTTALVVAQLLRIPQAILDMIAG AHWGVLAGIAYFSMVGNWAKVLVVLLLFAGVDAGTHVTGGSAAKDTSGFT SLFRIGARQNIQLINTNGSWHINSTALNCNASLDTGWIAGLFYYHKFNSS GCPERLASCRPLTDFDQGWGPISYANGSGPDQRPYCWHYPPKPCGIVPAK SVCGPVYCFTPSPVVVGTTDRSGAPTYSWGENDTDVFVLNNTRPPLGNWF GCTWMNSSGFTKVCGAPPCVIGGVGNNTLHCPTDCFRKHPEATYSRCGSG PWITPRCLVNYPYRLWHYPCTINYTIFKVRMYVGGVEHRLEAACNWTRGE RCDLDDRDRSELSPLLLSTTQWQVLPCSFTTLPALTTGLIHLHQNIVDVQ YLYGVGSSIASWAIKWEYVVLLFLLLADARVCSCLWMMLLISQAEAALEN LVILNAASLAGTHGLVSFLVFFCFAWYLKGRWVPGAVYALYGMWPLLLLL LALPQRAYALDTEVAASCGGVVLVGLMALTLSPYYKRYISWCLWWLQYFL TRVEAQLHVWVPPLNVRGGRDAVILLMCVVHPTLVFDITKLLLAVFGPLW ILQASLLKVPYFVRVQGLLRICALARKMAGGHYVQMAIIKLGALTGTYVY NHLTPLRDWAHNGLRDLAVAVEPVVFSQMETKLITWGADTAACGDIINGL PVSARRGQEILLGPADGMVSKGWRLLAPITAYAQQTRGLLGCIVTSLTGR DKNQVEGEVQIVSTAAQTFLATCINGVCWTVYHGAGTRTIASPKGPVIQM YTNVDKDLVGWPAPQGARSLTPCTCGSSDLYLVTRHADVIPVRRRGDGRG SLLSPRPISYLKGSSGGPLLCPAGHAVGIFRAAVCTRGVAKAVDFIPVEN LETTMRSPVFTDNSSPPAVPQSFQVAHLHAPTGSGKSTKVPAAYAAQGYT VLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTITTGSPITYSTYGKFL ADGGCSGGAYDIIICDECHSTDATSILGIGTVLDQAETAGARLTVLATAT PPGSITVPHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHLIFCHSKRKC DELAAKLVALGINAVAYYRGLDVSVIPASGDVVVVATDALMTGYTGDFDS VIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKPGIYR FVAPGERPSGMFDSSILCECYDAGCAWYELTPAETTVRLRAYMNTPGLPV CQDHLEFWEGVFTGLTHIDAHFLSQTKQSGENLPYLVAYQATVCARAQAL PPSWDQMWKCLTRLKPTLHGPTPLLYRLGAVQNEITLTHPVTKYIMTCMS ADLEVVTSTWVLVGGVLAALAAYCLSTGCVVIVGRIVLSGKPAIIPDREV LYREFDEMEECSQHLPYIEQGMMLAEQFKQKALGLLQTASRQAEVIAPAV QTNWQKLEAFWAKHMWNFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSP LTTSQTLLFNILGGWVAAQLAAPGAATAFVGAGLAGAAIGSVGLGKVLVD IIAGYGAGVAGALVAFKIMSGEVPSTEDLVNLLPAILSPGALVVGVVCAA ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVQESDAAARVTAILSS LTVTQLLRRLHQWISSECTTPCSGSWLRDIWDWICEVLSDFKTWLKAKLM PQLPGIPFVSCQRGYRGVWRGDGIMHTRCHCGAEITGHVKNGTMRIVGPR TCRNMWSGTFPINAYTTGPCTPLPAPNYTFALWRVSAEEYVEIRQVGDFH YVTGMTTDNLKCPCQVPSPEFFTELDGVRLHRFAPPCKPLLREEVSFRVG LHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAGRRLARGSPPSVAS SSASQLSAPSLKATCTANHDSPDAELIEANLLWRQEMGGNITRVESENKV VVLDSFDPLVAEEDEREISVPAEILRKSRRFAPALPIWARPDYNPPLLET WKKPDYEPPVVHGCPLPPPQSPPVPPPRKKRTVVLTESTVSTALAELATK SFGSSSTSGITGDNTTTSSEPAPSGCPPDSDAESYSSMPPLEGEPGDPDL SDGSWSTVSSGADTEDVVCCSMSYSWTGALVTPCAAEEQKLPINALSNSL LRHHNLVYSTTSRSACQRQKKVTFDRLQVLDSHYQDVLKEVKAAASKVKA NLLSVEEACSLTPPHSAKSKFGYGAKDVRCHARKAVNHINSVWKDLLEDS VTPIDTTIMAKNEVFCVQPEKGGRKPARLIVYPDLGVRVCEKMALYDVVS KLPLAVMGSSYGFQYSPGQRVEFLVQAWKSKKTPMGFSYDTRCFDSTVTE SDIRTEEAIYQCCDLDPQARVAIKSLTERLYVGGPLTNSRGENCGYRRCR ASGVLTTSCGNTLTCYIKARAACRAAGLQDCTMLVCGDDLVVICESAGVQ EDAASLRAFTEAMTRYSAPPGDPPQPEYDLELITSCSSNVSVAHDGAGKR VYYLTRDPTTPLARAAWETARHTPINSWLGNIIMFAPTLWARMILMTHFF SVLIARDQLEQALDCEIYGACYSIEPLDLPPIIQRLHGLSAFSLHSYSPG EINRVAACLRKLGVPPLRAWRHRARSVRARLLSRGGRAAICGKYLFNWAV KTKLKLTPIAAAGQLDLSGWFTAGYSGGDIYHSVSHARPRWFWFCLLLLA AGVGIYLLPNR

Design30.mosaic3_serial Amino Acid Sequence SEQ ID NO: 47 MSTNPKPQRKTKRNTNRRPQNVKFPGGGQIVGGVCLLPRRGPRVGVRATR KTSERSQPRGRRQPIPKARRPEGRSWAQPGYPWPLYGNEGCGWAGWLLSP RGSRPSRGPSDPRRRSRNLGKVIDTLTYGFADLMGYIPLVGAPLGGAARA LAHGVRVLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAVGVRNSSGV YHVTNDCPNASVVYETDSLIIHLPGCVPCVREGNGSRCWVSLSPTVAAKD PGVPVNEIRRHVDLIAGAAAFCSAMYVGHLCGSIFLVGQLFTLSPRRHWT TQDCNCSIYPGHVTGHRMAWDMMMNWSPTGALVVAQLLRIPQAVLDMIAG AHWGVLAGPAYYSMVGNWAKVVVVLLLFAGVDATTQVTGGTAGRNAYRLA SLFSTGPSQNIQLINSNGSWHINRTALNCNDSLHTGWVAALFYSHKFNSS GRPERMASCRPLTAFDQGWGPITHEGNASDDQRPYCWHYALRPCGIVPAK KVCGPVYCFTPSPVVVGTTDRAGVPTYRWGANETDVLLLNNSRPPMGNWF GCTWMNSSGFTKTCGAPACNVGGSETNTLSCPTDCFRRHPDATYAKCGSG PWLNPRCMVDYPYRLWHYPCTVNYTIFKIRMFVGGVEHRLDAACNWTRGE RCDLDDRDRAELSPLLLSTTQWQVLPCSFTTLPALSTGLIHLHQNIVDVQ YLYGLSSAVTSVVVIKWEYVVLLFLLLADARICACLWMMLLISQVEAALE NLIVLNAASLVGTHGIVPFFIFFCAAWYLKGKWAPGLAYSVYGMWPLLLL LLALPQRAYALDQELAASCGATVFICLAVLTLSPYYKQYMARGIWWLQYM LTRAEALLQVWVPPLNARGGRDGVVLLTCVLHPHLLFEITKIMLAILGPL WILQASLLRVPYFVRAHGLIRLCMLVRKTAGGHYVQMALLKLGALTGTYI YNHLSPLQDWAHSGLRDLAVATEPVIFSRMEIKTITWGADTAACGDIING LPVSARRGREVLLGPADALTDKGWRLLAPITAYAQQTRGLLGCIVTSLTG RDKNQVEGEIQIVSTATQTFLATCINGACWTVYHGAGSRTIASASGPVVR MYTNVDQDLVGWPAPQGARSLTPCTCGASDLYLVTRHADVIPVRRRGDNR GSLLSPRPISYLKGSSGGPLLCPMGHAVGIFRAAVCTRGVAKAVDFVPVE SLETTMRSPVFTDNSSPPTVPQSYQVAHLHAPTGSGKSTKVPAAYAAQGY KVLVLNPSVAATLGFGAYMSKAHGIDPNVRTGVRTITTGSPITHSTYGKF LADGGCPGGAYDIIICDECHSVDATSILGIGTVLDQAETAGVRLTVLATA TPPGLVTVPHSNIEEVALSADGEKPFYGKAIPLNYIKGGRHLIFCHSKKK CDELAAKLVGLGVNAVAFYRGLDVSVIPTTGDVVVVATDALMTGFTGDFD SVIDCNTCVVQTVDFSLDPIFSIETSTVPQDAVSRSQRRGRTGRGKHGIY RYVSPGERPSGMFDSVVLCECYDAGCAWYELTPAETTVRLRAYLNTPGLP VCQDHLEFWESVFTGLTHIDAHFLSQTKQSGENFPYLVAYQATVCARARA PPPSWDQMWKCLIRLKPTLTGATPLLYRLGSVQNEITLTHPITQYIMACM SADLEVVTSTWVLVGGVLAALAAYCLSTGSVVIVGRIILGGKPAVIPDRE VLYREFDEMEECAAHVPYLEQGMHLAEQFKQKALGLLQTASKQAETITPT VRTNWQKLESFWAKHMWNFVSGIQYLAGLSTLPGNPAIASLMSFTAAVTS PLTTQQTLLFNILGGWLAAQLAAPAAATAFVGAGITGAVVGSVGLGKVLV DILAGYGAGVAGALVAFKIMSGETPTTEDLVNLLPAILSPGALVVAVVCA AILRRHVGLGEGAVQWMNRLIAFASRGNHVSPTHYVPESDASARVTQILT SLTVTQLLKRLHVWISSDCIAPCASSWLKDVWDWICEVLSDFKNWLKAKL VPQLPGIPFVSCQRGYRGVWRGEGIVHTRCPCGANITGHVKNGSMRIVGP KTCSNTWRGSFPINAHTTGPCTPSPAPNYTFALWRVSAEEYVEVRRLGDF HYVTGVTTDKLKCPCQVPSPEFSTEVDGVRLHRYAPPCKPLLRDEVTFSI GLNEYLVGSQLPCEPEPDVAALTSMLTDPSHITAETAARRLKRGSPPSLA SSSASQLSAPSLKATCTTHHDSPDADLIEANLLWRREMGGNITRVESENK IVVLDSFDPLVAEEDDREISIPAEILRKFKQFPPAMPIWARPDYNPPLVE PWKRPDYEPPLVHGCPLPPPKPTPVPPPRRKRTVVLDESTVSSALAELAT KTFGSSTTSGVTSGEAAESSPALSCDGELDSEAESYSSMPPLEGEPGDPD LSDGSWSTVSSDGGTEDVVCCSMSYSWTGALITPCAAEETKLPINALSNS LLRHHNLVYSTTSRSAGQRQKKVTFDRVQVLDDHYRDVLKEAKAKASTVK ARLLSVEEACSLTPPHSARSKFGYGPKDVRSHSSKAIRHINSVWQDLLED NTTPIDTTIMAKNEVFCVKPEKGGRKPARLIVYPDLGVRVCEKRALYDVV KQLPIAVMGPSYGFQYSPAQRVDFLLNAWKSKKNPMGFSYDTRCFDSTVT EADIRTEEDLYQSCDLVPEARAAIRSLTERLYIGGPLTNSKGQNCGYRRC RASGVLTTSCGNTITCYLKASAACRAAKLRDCTMLVCGDDLVVICESAGV KEDAASLRAFTEAMTRYSGPPGDPAQPEYDLELITSCSSNVSVARDGAGK RVYYLTRDPETPLARAAWETARHTPVNSWLGNIIMFAPTLWVRMVLMTHF FSILIAQEHLEKALDCEIYGAVHSVQPLDLPEIIQRLHSLSAFSLHSYSP GEINRVAACLRKLGVPPLRAWRHRARSVRATLLSQGGKAAICGKYLFNWA VKTKLKLTPLPSMSQLDLSNWFTGGYSGGDIYHSVSHVRPRWFFWCLLLL SVGVGIYLLPNR

Design30.mosaic4_serial Amino Acid Sequence SEQ ID NO: 48 MSTNPKPQRKIKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRAPRKT SERSQPRGRRQPIPKARRPEGRAWAQPGYPWPLYGNEGLGWAGWLLSPRG SRPSWGPNDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGVARALAHGV RVVEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSSGLYHVTNDCSN ASIVYEAADVIMHTPGCVPCVREGNSSRCWVALTPTLAARNSSIPTTTIRRHVDL LVGAAALCSAMYVGDFCGSVFLVSQLFTFSPRRYETVQDCNCSLYPGHVSGH RMAWDMMMNWSPTAALVVSQLLRIPQAIMDMVAGAHWGVLAGLAYYSMAGN WAKVLIVMLLFAGVDGGTHVTGGKVAYTTQGFTSFFSRGPSQKIQLVNTNGSW HINRTALNCNDSLNTGFLAALFYTHKFNASGCPERMASCRSIDKFDQGWGPITY AEPHDLDQRPYCWHYPPQPCGIVPAAQVCGPVYCFTPSPVVVGTTDRSGAPT YNWGENETDVFILNNTRPPQGNWFGCTWMNGTGFTKTCGGPPCNIGGAGNN TLICPTDCFRKHPEATYAKCGSGPWLTPRCLVHYPYRLWHYPCTVNFTVFKVR MYVGGVEHRLHAACNWTRGERCNLEDRDRSELSPLLLSTTEWQVLPCSFTTL PALSTGLIHLHRNIVDVQYLYGVGSSIVSWAIKWEYVILLFLLLADARICSCLWMM LLISQAEAALENLVVLNAASVAGTHGILSLLVFFCAAVVYIKGKLVPGAAYAFYGV WPLLLLLMALPARAYAMDREMAASCGGAVFVGLVLLTLSPYYKVFLAKLIWWL QYFITRAEAHLQVWVPPLNVRGGRDAIILLTCAIHPELIFTITKILLAILGPLMVLQA GLTQMPYFVRAQGLIRACMLVRKAAGGHYVQMALMKLAALTGTYVYDHLTPLQ DWAHVGLRDLAVAVEPVIFSDMETKIITWGAETAACGDIISGLPVSARRGKEILL GPADSFGEQGWRLLAPITAYSQQTRGLFGCIITSLTGRDRNQVEGEVQVVSTA TQSFLATCINGVCWTVFHGAGSKTLAGPKGPVTQMYTNVDQDLVGWPAPPGA RSMTPCTCGSSDLYLVTRHADWPVRRRGDSRGSLLSPRPVSYLKGSSGGPLL CPSGHVVGIFRAAVCTRGVAKAVDFIPVESMETTMRSPVFTDNSSPPVVPQSF QVAYLHAPTGSGKSTRVPAAYAAQGYKVLVLNPSVAATLSFGAYMSKAYGTDP NIRTGVRTITTGASITYSTYGKFLADGGCSGGAYDIIMCDECHSTDSTSILGIGTV LDQAETAGARLVVLATATPPGSVTVPHSNIEEVALSNIGEIPFYGKAIPIEAIKGG RHLIFCHSKKKCDELAAKLSALGVNAVAYYRGLDVSVIPTSGNVVVVATDALMT GYTGDFDSVIDCNTCVIQTVDFSLDPTFTIDTTTVPQDAVSRTQRRGRTGRGRG GIYRFVTPGERPSGMFDSSVLCECYDAGCAVVYELTPAVTSVRLRAYLNTPGLP VCQVHLEFWESVFTGLTHIDAHFLSQTKQAGENFPYLTAYQATVCARSQAPPP SWDQMWKCLIRLKPTLHGATPLLYRLGAVQNEITLTHPITKFIMACMSADLEIVT STVVVLVGGVLAALAAYCLSTGCVVIVGRVVLSGKPAIIPDREVLYKEFDEMEEC SQHLPYIEQGMALAEQFKQKALGLLQTASRQAEVITPAVQTNWQKLEVFWAKH MWNFISGVQYLAGLSTLPGNPAIASLMAFTASVTSPLTTQSTLLFNILGGVVVAA QLAPPSAASAFVGAGIAGAAIGSIGLGKVLVDILAGYGAGVAGALVAFKVMSGD MPSTEDLVNLLPAILSPGALWGVVCAAILRRHVGPGEGAVQWMNRLIAFASRG NHVSPTHYVPESDAAARVTTILSSLTVTQLLRRLHQWISSDCTTPCSGSWLKDV WDWICTVLSDFKTWLQTKLLPRLPGVPFLSCQRGYKGVWRGDGIMHTTCPCG AQIAGHVKNGSMRIVGPRTCSNTWHGTFPINAYTTGPCVPSPAPNYSKALWRV AAEEYVEVTRVGDSHYVTGMTTDNIKCPCQVPAPEFFTELDGVRLHRYAPACK PLLRDEVTFQVGLNQYVVGSQLPCEPEPDVTVLTSMLTDPSHITAEAARRRLAR GSPPSLARSSASQLSAPSLKATCTTRHDSPDADLIEANLLWRQEMGGNITRVES ENKWILDSFEPLRAEEDEREVSVAAEILRKTRKFPAAMPVWARPDYNPPLIES WKDPDYVPPVVHGCPLPPIKAPPIPPPRRKRTVVLSESTVSSALAELATKTFGS SGSSAVDSGTATAPPDQASDDGDKGSDVESYSSMPPLEGEPGDPDLSDGSW STVSSEAGTEDVVCCSMSYTWTGALITPCAAEESKLPINPLSNSLLRHHSMVYS TTSRSASLRQKKVTFDRLQVLDNHYQDVLKEMKAKASTVKAKLLSIEEACKLTP PHSAKSKFGYGAKDVRSLSSRAVNHIRSVWEDLLEDTETPIDTTIMAKSEVFCV QPEKGGRKAARLIVFPDLGVRVCEKMALYDVVSKLPLAVMGSSYGFQYSPKQR VEFLVNTWKSKKCPMGFSYDTRCFDSTVTESDIRVEESIYQCCDLAPEARQAIK SLTERLYIGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKAQAACRAAGL RDCTMLVNGDDLVVICESAGTQEDEASLRVFTEAMTRYSAPPGDPPKPEYDLE LITSCSSNVSVAHDATGKRVYYLTRDPATPLARAAWETVRHTPVNSWLGNIIMY APTLWARMVLMTHFFSILLAQEQLDKALDCQIYGATYSIEPLDLPQIIERLHGLSA FSLHSYSPGEINRVAACLRKLGVPPLRVWRHRARSVRARLLSQGGRAAICGRY LFNWAVKTKLKLTPIAAASQLDLSGWFTAGYSGGDIYHSVSRARPRWFMLCLLL LSVGVGIYLLPNR

Design32.mosaic1 Amino Acid Sequence SEQ ID NO: 49 MSTLPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRAVRKT SERSQPRGRRQPIPKARQPQGRHWAQPGYPWPLYGNEGMGWAGWLLSPRG SRPNWGPNDPRRRSRNMGKVIDSLTCGFADLMGYIPVLGAPLGGVAAALAHG VRAIEDGINYATGNLPGCSFSIFLLALLSCLTTPASALTYGNSSGLYHLTNDCPN SSIVLEADAMILHLPGCLPCVRVDNRSTCWHAVSPTLAIPNASTPATGFRRHVD LLAGAAWCSSLYIGDLCGSLFLAGQLFTFQPRRHWTVQDCNCSIYTGHVTGH RMAWDMMMNWSPTTTLVLSSILRVPEICASVIFGGHWGILLAVAYFGMAGNWL KVLAVLFLFAGVEATTTIGHEVGRASATLAGMFSSGARQNLQLINTNGSWHINS TALNCNDSLQTGFIASLFYAHRFNSSGCPERMAACKPLADFRQGWGQITYKVNI SGPSDDRPYCWHYAPRPCGIVPASEVCGPVYCFTPSPWVGTTDRSGVPTYN WGENETDVFMLESLRPPTGGWFGCTWMNSSGFTKTCGAPPCQIVPGDYNSS ANELLCPTDCFRKHPEATYQRCGSGPWLTPRCLVDYPYRLWHYPCTVNFTLH KVRMFVGGIEHRFDAACNWTRGERCELHDRDRIEMSPLLFSTTQLAILPCSFTT MPALSTGLIHLHQNIVDVQYLYGVSSSVTSVVVVKWEYIVLMFLVLADARICTCL WLMLLISNVEAAVERLVVLNAASAAGTAGWWWAVLFLCCVWYVKGRLVPACT YMALGMWPLLLTILALPPRAYAMDNEQAASLGAVGLLVITIFTITPMYKKLLTCFI WWNQYFLARAEAMIHEWVPDLRVRGGRDSIILLTCLLHPQLGFEVTKILLAILAP LYILQYSLLKVPYFVRAHILLRACLLVRRLAGGKYVQACLLRLGAWTGTFVYDHL TPLSDWASDGLRDLAVAVEPVIFSPMEKKVITWGADTAACGDILSGLPVSARLG NLVLLGPADDMQRGGWKLLAPITAYAQQTRGLVGTIVTSLTGRDKNEVEGEVQ VVSTATQSFLATSINGVMWTVYHGAGSKTLAGPKGPVCQMYTNVDQDLVGWP APQGTRSLTPCTCGSSDLYLVTREADVIPARRRGDNRAALLSPRPISTLKGSSG GPIMCPSGHVVGLFRAAVCTRGVAKSLDFIPVENMETTMRSPSFTDNSTPPAV PQSYQVGYLHAPTGSGKSTRVPAAYASQGYKVLVLNPSVAATLSFGSYMRQA YGVEPNVRTGVRTITTGGAITYSTYGKFFADGGCSGGAYDVIICDECHSTDPTT VLGIGTVLDQAETAGCRLTVLATATPPGSITVPHPNITESALPTTGEVPFYGKAIP IEVIKGGRHLIFCHSKKKCDELAKQLTSLGLNAVAFYRGVDVSVIPTSGDVWCA TDALMTGFTGDFDSVIDCNVSVTQWDFSLDPTFSIETTTVPQDAVSRTQRRGR TGRGKPGVYRFVSQGERPSGMFDTVVLCEAYDTGCAVVYELSPSETTVRLRAY LNTPGLPVCQDHLEFWEGVFTGLTHIDAHFLSQTKQGGENFAYLTAYQATVCA RALAPPPSWDTMWKCLIRLKPTLTGPTPLLYRLGAVQNEIITTHPITKYIMTCMS ADLEVITSTWVLVGGVLAALAAYCLSVGCWICGRITLTGKPAWPDREILYQQF DEMEECSRHIPYLAEGQQIAEQFRQKVLGLLQASAKQAEELKPAVHSAWPKLE QFWQKHLWNFVSGIQYLAGLSIWPGNPAVASLMSFSASLTSPLSTSTTLLLNIL GGWIATQVAPPPASTAFVVSGLAGATVGSIGLGRVLVDVLAGYGAGVSGALVA FKIMSGECPTTEDMVNLLPALLSPGALWGVVCPAILRRHVGPAEGANQWMNR LIAFASRGNHGSPTHYVPETDASKNVTQILTSLTITSLLRRLHQWVNEDTATPCA TSWLRDVWDVVVCTVLSDFKVWLQAKLLPRLPGIPFLSCQTGYRGVWAGDGVC HTTCTCGAVIAGHVKNGTMKITGPKTCSNTWHGTFPINATTTGPSTPRPAPNYQ RALWRVSAEDYVEVRRLGDCHYWGVTAEGLKCPCQVPAPEFFTEVDGVRIH RYAPPCKPLLRDEVTFSVGLSNYAIGSQLPCEPEPDVTWTSMLTDPTHITAETA ARRLKRGSPPSLASSSASQLSAPSLKATCTTSKDHPDMELIEANLLWRQEMGS NITRVESENKVWLDSFEPLTAEYDEREISVSAECHRPPRHKFPPALPIWARPDY NPPLLQAWQMPGYEPPWSGCAVAPPKPAPIPPPRRKRLVHLDESTVSHALAQ LADKVFVESSNDPGPSSDSGLSITSPVPPAPSTPDDACSEAESYSSMPPLEGE PGDPDLSSGSWSTVSDQDDVVCCSMSYTWTGALITPCAAEEEKLPINPLSNSLI RHHNMVYSTTSRSASLRQKKVTFDRVQVFDQHYQDVLKEIKLRASTVQARLLSI EEACDLTPSHSARSKYGYGAQDVRSHASKAINHIRSVWEDLLEDSDTPIPTTIM AKNEVFCVDPSKGGRKPARLIVYPDLGVRVCEKMALYDVTQKLPQAVMGSAY GFQYSPNQRVEYLLKMWRSKKVPMGFSYDTRCFDSTVTERDIRTENDIYQSCQ LDPVARKAVSSLTERLYVGGPMFNSKGQTCGYRRCRASGVLPTSMGNTITCYL KAQAACRAANIKDCDMLVCGDDLVVICESAGVQEDTASLRAFTDAMTRYSAPP GDAPQPTYDLELITSCSSNVSVAHDGNGKRYYYLTRDCTTPLARAAWETVRHS PVNSWLGNIIMFAPTIVVVRMVLMTHFFSILQSQEQLEKALDFDIYGVTYSVSPLD LPAIIQRLHGMAAFSLHGYSPGELNRVAACLRKLGAPPLRAWRHRARAVRAKLI AQGGKAAICGKYLFNWAVRTKLKLTPLVSASKLDLSGWFVAGYDGGDIYHSVS QARPRLLLLGLLLLTVGVGIFLLPAR

Design32.mosaic2 Amino Acid Sequence SEQ ID NO: 50 MSTNPKPQRITKRNINRRPQDVKFPGGGVIYVGVYVLPRRGPKLGVRATRKTS ERPQPRGRRQPIPKARRSEGRSWAQPGYPWPLYGNEGCGWAGWLLSPRGS RPTWGPTDPRHRSRNLGKVIDTLTCGLADLMGYIPVVGAPVGGVARALAHGVR AVEDGINYATGNLPGCSFSIFLLALLSCVTVPVSAVEVRNISSSYYATNDCSNNSI TWQLTNAVLHLPGCVPCENDNGTLRCWIQVTPNVAVKHRGALTHNLRTHVDMI VMAATVCSALYVGDVCGAVMIVSQALIVSPERHNFTQECNCSIYQGHITGHRMA WDMMLNWSPTLTMILAYAARVPELVLEIVFGGHWGVVFGLAYFSMQGAWAKVI AILLLVAGVDATTYSTGAQAGRGASGIANLFTPGAKQNIQLINTNGSWHINRTAL NCNASLDTGWVAGLFYYHKFNSSGCPERMSSCRGLDDFRIGWGTLEYETNVT NDEDMRPYCWHYPPKPCGIVPARSVCGPVYCFTPSPVWGTTDRLGVPTYTW GENETDVFLLNSTRPPRGAWFGCTWMNSTGFTKTCGAPPCRIRADFNASTDLL CPTDCFRKHPDATYLKCGAGPWLTPRCLVNYPYRLWHYPCTVNFTIFKVRMYV GGVEHRLSAACNFTRGDRCRLEDRDRGQQSPLLHSTTEWAVLPCSFSDLPAL STGLLHLHQNIVDVQYLYGVGSAVVSWALKWEYVVLAFLLLADARVCACLWMLI ILGQAEAALEKLIILHSASAASANGPLWFFIFFTAAWYLKGRVVPVATYSVLGLW SFLLLVLALPQQAYALDAAEQGELGLVILVIISIFTLTPAYKILLSRSVWWLSYMLV LAEAQIQQWVPPLEARGGRDGIIVVVAVILHPRLVFEVTKWLLALLGPAYLLKASL LRVPYFVRAHALLRVCTLVRHLAGARYIQMLLITIGRWTGTYIYDHLSPLSTWAA QGLRDLAVAVEPIIFSPMEKKVIVWGAETVACGDILHGLPVSARLGREVLLGPAD GYTSKGWKLLAPITAYSQQTRGLLGAIWSMTGRDKTEQAGEIQVLSTVTQSFL GTSISGVLWTVYHGAGNKTLAGSRGPVTQMYSSAEGDLVGWPSPPGTKSLEP CTCGAVDLYLVTRNADVIPARRRGDKRGALLSPRPLSTLKGSSGGPVLCPRGH AVGIFRAAVCSRGVAKSIDFIPVETLDIVTRSPTFSDNSTPPAVPQTYQVGYLHA PTGSGKSTKVPVAYAAQGYKVLVLNPSVAATLGFGAYLSKAHGINPNIRTGVRT VTTGGAITYSTYGKFLADGGCAGGAYDIIICDECHSVDATTILGIGTVLDQAETAG VRLTVLATATPPGSVTTPHPNIEEVALGQEGEIPFYGRAIPLSYIKGGRHLIFCHS KKKCDELAAALRGMGLNAVAYYRGLDVSVIPTQGDWWATDALMTGFTGDFD TVIDCNVAVTQVVDFSLDPTFTIETTTMPQDAVSRSQRRGRTGRGRGGIYRFVT PGERPSAMFDSSVLCECYDTGCAWYELTPSETTVRLRAYFNTPGLPVCQDHLE FWEAVFTGLTHIDAHFLSQTKQSGENFPYLVAYQATVCARAKAPPPSWDVMW KCLTRLKPTLVGPTPLLYRLGSVTNEVTLTHPVTKYIATCMQADLEVMTSTWVL AGGVLAAVAAYCLATGCVSIIGRLHINQRAWAPDKEVLYEAFDEMEECASRAA LIEEGQRIAEMLKSKIQGLLQQASKQAQDIQPAIQSSWPKLEQFWAKHMWNFV SGIQYLAGLSTLPGNPAVASMMAFSAALTSPLSTSTTILLNIMGGWLASQIAPPA GATGFVVSGLVGAAVGSIGLGKILVDVLAGYGAGISGALVAFKIMSGEKPSVED WNLLPAILSPGALWGVICAAILRRHVGQGEGAVQWMNRLIAFASRGNHVAPT HYVAESDASQRVTQVLSSLTITSLLRRLHAWITEDCPVPCSGSWLRDIWDWVC SILTDFKNWLTSKLFPKMPGLPFISCQKGYRGVWAGTGIMTTRCPCGANISGNV RLGSMRITGPKTCMNTWQGTFPINCYTEGQCVPKPAPNFKTAIWRVAASEYVE VTQHGSFSYVTGLTSDNLKVPCQLPSPEFFSWVDGVQIHRFAPTPKPFFRDEV SFCVGLNSFWGSQLPCDPEPDTEVLASMLTDPSHITAEAAARRLARGSPPSQ ASSSASQLSAPSLRATCTTHGKTYDVDMVDANLFMGGDVTRIESDSKVIVLDSL DSMTEVEDDREPSVPSEYLIRRRKFPPALPPWARPDYNPPVIETWKRPGYEPP TVLGCALPPTPQAPVPPPRRRRAKVLTQDNVEGVLREMADKVLSPLQDHNDS GHSTGADTGGDSVQQPSDETAASEAGSLSSMPPLEGEPGDPDLEFEPAGSAP PSEGECEVIDSDSKSWSTVSDQEDSVICCSMSYSWTGALITPCGPEEEKLPISP LSNSLMRFHNKVYSTTSRSASLRAKKVTFDRVQVLDAHYDSVLKDIKLAASKVS ARLLSVEEACALTPPHSAKSKFGYGAKDVRSHSRKAINHINSVWEDLLEDQHTP IDTTIMAKNEVFCVDPTKGGKKAARLIVYPDLGVRVCEKRALYDIAQKLPKAVMG PSYGFQYSPAQRVDFLLNAWKSKKNPMGFSYDTRCFDSTVTERDIRTEESIYQ ACSLPQEARTVIHSLTERLYVGGPMTNSKGQSCGYRRCRASGVFTTSMGNTM TCYIKALAACKAAGIVDPIMLVCGDDLWISESQGNEEDERNLRAFTEAMTRYSA PPGDLPRPEYDLELITSCSSNVSVALDSRGRRRYFLTRDPTTPIARAAWETVRH SPVNSWLGNIIQYAPTIWVRMVIMTHFFSILLAQDTLNQNLNFEMYGAVYSVNPL DLPAIIERLHGLDAFSLHTYSPHELSRVAATLRKLGAPPLRAWKSRARAVRASLI AQGGRAAICGRYLFNWAVKTKLKLTPLPEASRLDLSGWFTVGAGGGDIFHSVS HARPRLLLLCLLLLSVGVGIFLLPAR

Design32.mosaic3 Amino Acid Sequence SEQ ID NO: 51 MSTNPKPQRQTKRNTNRRPQNVKFPGGGQIVGGVYLLPRKGPRLGVRAPRKT SERSQPRGRRQPIPKDRRSTGKSWGKPGYPWPLYGNEGLGWAGWLLSPRGS RPSWGPNDPRHRSRNVGKVIDTLTCGFADLMGYIPVVGAPLGGVARALAHGV RALEDGINFATGNLPGCSFSIFLLALLSCLTIPASAIEVRNVSGVYHVTNDCSNAS IVYEAADMIMHTPGCVPCVREGNSSRCWVALTPTLAARNSSIPTTTIRRHVDLLV GTAAFCSAMYVGDLCGSVFLVSQLFTFSPRRYETVQDCNCSIYPGHVSGHRM AWDMMMNWSPTTALWSQLLRIPQAWDMVAGAHWGVLAGLAYYSMVGNWA KVLIVMLLFAGVDGNTHVTGGQAGQHAIRFTSLFSSGASQKIQLVNSNGSWHIN RTALNCNDSLQTGFLAALFYTHRFNASGCPERMASCRPIDKFAQGWGPITYAE PPDLDQKPYCWHYAPQPCGIVPASQVCGPVYCFTPSPVVVGTTDRFGVPTYS WGENETDVLLLNNTRPPRGNWFGCTWMNGTGFTKTCGGPPCNIGGVGNDTLI CPTDCFRKHPEATYAKCGSGPWLTPRCMVDYPYRLWHYPCTLNFSIFKIRMYV GGVEHRLNAACNWTRGERCDLEDRDRSELSPLLLSTTEWQILPCSFTTLPALS TGLIHLHRNIVDVQYLYGIGSAVVSFAIKWEYVLLLFLLLADARVCACLWMMLLIA QAEAALENLVVLNAASVAGTHGILSFLVFFCAAVVYIKGRLVPGAAYALYGVWPL LLLLLALPPRAYAMDREMAASCGGAVFIGLALLTLSPHYKVFLARLIWWSQYLIT RAEAHLQVWVPPLNVRGGRDAIILLMCAIHPELIFTITKILLAILGPLMVLQAGITR VPYFVRAHGLIRACMLVRKAAGGHYVQMALMKLAALTGTYVYDHLTPLRDWAH AGLRDLAVAVEPWFSDMETKVITWGADTAACGDIILGLPVSARRGREILLGPAD SLEGQGWRLLAPITAYAQQTRGLLGTIVTSLTGRDTNENCGEVQVLSTATQSFL ATCVNGVCWTVYHGAGTKTLAGQKGPITQMYTNVDQDLVGWPAPPGARSMT PCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPLLCPSGH WGIFRAAVCTRGVAKAVDFVPVESMETTMRSPVFTDNSTPPAVPQTYQVAHL HAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGVDPNIRTG VRTITTGSSITYSTYGKFLADGGCSGGAYDIIMCDECHSTDSTSILGIGTVLDQAE TAGVRLVVLATATPPGSVTVPHPNIEEVALSNTGEIPFYGKAIPLEAIKGGRHLIF CHSKKKCDELAAKLSALGVNAVAYYRGLDVSIIPTSGDVVVVATDALMTGYTGN FDSVIDCNVAVTQIVDFSLDPTFTITTQTVPQDAVSRSQRRGRTGRGRLGIYRY VSSGERPSGMFDSWLCECYDAGAAWYELTPAETSVRLRAYLNAPGLPVCQD HLEFWEGVFTGMTHIDAHFLSQTKQAGDNFPYLVAYQATVCARAQAPPPSWD QMWKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKFIMACMSADLEVATST VVVLVGGVLAALAAYCLSVGSVVIVGRIILSGRPAVIPDREVLYQQFDEMEECAT HLPYIEQGMQLAEQFKQKALGLLQTASKQAEAAAPVVESKWRALESFWAKHM WNFISGIQYLAGLSTLHGNPAIASLMAFTASITSPLTTQHTLLFNILGGVVVAAQLA PPSAASAFVGAGIAGAAVGSIGLGKVLVDILAGYGAGVAGALVAFKVMSGEMPS TEDLVNLLPALLSPGALWGWCAAILRRHAGPAEGATQWMNRLIAFASRGNHV SPTHYVPESDAAARVTQILSSLTITQLLKRLHQWINEDCSTPCSGSWLRDVWD WICTVLSDFKTWLQSKLLPRLPGVPFLSCQRGYKGVWRGDGVMQTTCPCGAQ IAGHVKNGSMRIVGPRTCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAA EEYVEVTRVGDFHYVTGMTADNIKCPCQVPAPEFFTELDGVRLHRYAPACRPL LRDEVTFQVGLNQYPVGSQLPCEPEPDVSVLTSMLRDPSHITAEAARRRLARG SPPSEASSSASQLSAPSLKATCTTRHDSPDADLIEANLLWRQEMGGNITRVESE TKWILDSFEPLRAEEDEREVSVPAEILRRSRKFPRAMPIWARPDYNPPLVESW KDPDYVPPVVHGCPLPPAKAPPIPPPRRKRTWLTESTVSSALAELATKTFGSS ESSAVDSGTATAPPDQPSDDGDAGSDVGSYSSMPPLEGEPGDPDLSDGSWS TVSEEASEDVVCCSMSYTWTGALITPCSAEESKLPINALSNSLLRRHNMVYATT SRSASQRQKKVTFDRMQVLDDHYRDVLKEMKAKASTVKAKLLSVEEACKLTPP HSARSKFGYGAKDVRNLSSKAVNHIRSVWKDLLEDTETPLDTTVMAKNEVFCV QPEKGGRKPARLIVYPDLGVRVCEKMALYDVTRKLPQAVMGASYGFQYSPGQ RVEFLVNAWKSKKSPMGFAYDTRCFDSTVTESDIRVEESIYQCCDLAPEARQAI RSLTERLYIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYIKAQAACRAA GLRDCTMLVCGDDLWICESAGVQEDAASLRAFTEAMTRYSAPPGDPPRPEYD LELITSCSSNVSVAHDGTGQRYYYLTRDPTGPLARAAWETARHTPVNSWLGNII MYAPTIVVVRMVLOTHFFQILQAQEQLHKALDFDMYGVTYSITPLDLPQIIQRLHG LSAFTLHSYSPGEINRVAACLRKLGVPPLRVWRHRARSVRARLLSQGGRAATC GKYLFNWAVKTKLKLTPIAAASQLDLSGWFVAGYSGGDIYHSVSRARPRWFM WCLLLLSVGVGLFLLPAR

Design32.mosaic4 Amino Acid Sequence SEQ ID NO: 52 MSTNPKPQRKTQRNTNRRPTDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGMGWTGWLLSPRG SRPSWGPTDPRRRSRNLGKVIDTITCGFADLMGYIPVLGGPLGGVAAALAHGV RVLEDSVNYATGNLPGCPFSIFLLALLSCLTIPASAYEVRNVSGIYHVTNDCSNS SIVYEADHHILHLPGCVPCVRENNSSRCVVVALTPTLAARNASVPTTTIRRHVDLL VGAAAFCSAMYVGDLCGSVFLISQLFTFSPRRHETVQDCNCSIYPGTITGHRMA WDMMMNWSPTATMILAYAMRVPEVIIDIISGAHWGVMFGLAYFSMQGAWAKV WILLLAAGVDARTHTVGGSAAQTTGRLTSLFDMGPRQKIQLVNTNGSWHINRT ALNCNDSLNTGFLAALFYTHKFNASGCPERMASCRPLADFDQGWGPISHWPN ISDQRPYCWHYAPRPCSVVSASTVCGPVYCFTPSPWVGTTDRFGAPTYSWG ENETDVLLLNNTRPPQGNWFGCTWMNGTGFTKTCGVPPCNIGGVGNNTLTCP TDCFRKHPEATYTKCGSGPWLTPRCIVDYPYRLWHYPCTINYTIFKVRMYVGG VEHRLDAACNWTRGERCNLEDRDRSELSPLLLSTTEWQVLPCSFTTLPALSTG LIHLHQNWDVQYLYGVGSSIVSWAIKWEYVILLFLLLADARICSCLWMMLLISQA EAALENLVILNAASVAGAHGILSFLVFFCAAVVYIKGKLVPGAAYAFYGVWPLLLL LLALPPRAYALDREMAASCGGAVFVGLVLLTLSPYYKVFLARLIWWLQYFITRAE AHLQVWIPPLNVRGGRDAIILLTCAVHPELIFDITKLLLAILGPLMVLQAGMTRVP YFVRAQGLIRACMLVRKVAGGHYVQMAFMKLAALTGTYVYDHLTPLQDWAHT GLRDLAVAVEPVVFSDMETKIITWGADTAACGDIISGLPVSARRGKEILLGPADS FGEQGWRLLAPITAYSQQTRGLLGCIVTSLTGRDKNQVEGEVQVVSTATQSFL ATCINGVCWTVFHGAGSKTLAGPKGPITQMYTNVDQDLVGWQAPPGARSLTP CTCGASDLYLVTRNADVIPVRRRGDGRGSLLSPRPVSYLKGSSGGPLLCPSGH AVGIFRAAVCTRGVAKAVDFIPVESLETTMRSPVFTDNSSPPAVPQTFQVAHLH APTGSGKSTKVPAAYVAQGYSVLVLNPSVAATLGFGAYMSKAYGIDPNIRSGV RTITTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSTDSTTILGIGTVLDQAETA GARLWLATATPPGTVTTPHSNIEEVALGHEGEIPFYGKAIPIETIKGGRHLIFCH SRKKCDELAAKLSGLGLNAVAYYRGLDVSVIPTSGNWWATDALMTGYTGDF DSVIDCNTCVTQTVDFSLDPTFTIETTTVPQDAVARSQRRGRTGRGRRGIYRFV TPGERPSGMFDSSVLCECYDAGAAWYELTPAETTTRLRAYFNTPGLPVCQDHL EFWESVFTGLTHIDAHFLSQTKQAGENFAYLVAYQATVCARAKAPPPSWDQM WKCLTRLKPTLHGPTPLLYRLGSVQNEVTLTHPITKYIMACMSADLEVVTSTWV LVGGVLAALAAYCLTTGSVVIVGRIILSGKPAVIPDREVLYQEFDEMEECASHLP YIEQGMQLAEQFRQKALGLLQTATKQAEAAAPVVESKWRALETFWAKHMWNFI SGIQYLAALSTLPGNPAVASLMAFTASVTSPLTTQSTLLFNILGGVVVASQLANPT ASTAFWSGLAGAAVGSVGLGKILVDILAGYGAGISGALVAFKIMSGEKPSMEDV VNLLPGILSPGALWGVVCAAVLRRHVGPSEGAAQWMNRLIAFASRGNHVAPT HYVTESDASQRVTQLLGSLTITSLLRRLHNWITEDCPIPCAGSWLRDVWDWICT VLTDFKTWLQSKLMPRLPGVPFFSCQRGYKGVWRGDGIMQTTCPCGAQITGH VKNGSMRIVGPKTCSNTWHGTFPINAYTTGPGVPVPAPNYKFALWRVSAEEYV EVRRVGDFHYVTGMTTDNVKCPCQVPAPEFFTEVDGVRLHRYAPACKPLLRE EVTFQVGLNQYLVGSQLPCEPEPDVTVLTSMLTDPSHITAETAKRRLARGSPPS LARSSASQLSAPSLKATCTTHHDSPDADLIEANLLWRQEMGNNITRVESENKVV ILDSFDPLRAEEDEREVSVAAEILRKSRKFPPALPVWARPDYNPPLLESWKDPD YVPPVVHGCPLPPTKAPPIPPPRRKRTVVLTESNVSSALAELATKTFGSSGSSA VDSGTATAPPDQASDDGDKGSDVESYSSMPPLEGEPGDPDLEPEQVELQPPP QGGEVAPGSDSGSWSTCSEEDDSWCCSMSYSWTGALITPCAAEESKLPINPL SNSLLRHHNMVYATTSRSAGLRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVK AKLLSIEEACKLTPPHSAKSRYGFGAKEVRSLSRRAVNHIRSVWEDLLEDTETPI DTTIMAKSEVFCVQPEKGGRKPARFIVFPDLGVRVCEKMALYDVVSTLPQAVM GSSYGFQYSPKQRVEFLVNTWKSKKCPMGFSYDTRCFDSTVTENDIRVEESIY QCCDLAPEARQAIKSLTERLYIGGPLTNSKGQSCGYRRCRASWLTTSCGNTLT CYLKASAACRAAKLQDCTMLVNGDDLVVICESAGTQEDAASLRVFTEAMTRYS APPGDPPKPEYDLELITSCSSNVSVAHDASGKRVYYLTRDPETPLARAAWETA KHTPVNSWLGNIIMYAPTLWARMILMTHFFSILLAQEQLEKALDCQIYGACYSIE PLDLPQIIERLHGLSAFSLHSYSPGEINRVASCLRKLGVPPLRAWRHRARSVRA KLLSQGGRAANCGKYLFNWAVKTKLKLTPIPAASQLDLSSWFVAGYSGGDIYH SLSRARPRWFMLCLLLLSVGVGIYLLPNR

Design32.mosaic5 Amino Acid Sequence SEQ ID NO: 53 MSTNPKPQRKTKRNTNRRPMDVKFPGGGQIVGGVYVLPRRGPRLGVRAARKT SERSQPRGRRQPIPKARQPEGRAWAQPGYPWPLYANEGLGWAGWLLSPRGS RPHWGPNDPRRRSRNLGKVIDTITCGFADLMGYIPLVGAPLGGAARALAHGVR VLEDGVNYATGNLPGCSFSVFLLALLSCLTVPASAYQVRNSTGLYHVTNDCPN SSIVYEAADAILHTPGCVPCVREGNASRCVVVAVTPTVATRDGKLPTTQLRRHID LLVGSATLCSALYVGDLCGSVFLVGQLFTFSPRRHWTTQGCNCSIYPGHITGHR MAWDMMMNWSPTAALVVAQLLRIPQAILDMIAGAHWGVLAGIAYFSMVGNWA KVLVVLLLFAGVDAETHVTGGSAGHTTAGLVRLLSPGAKQNIQLINTNGSWHIN RTALNCNESLNTGWLAGLFYHHKFNSSGCPERLASCRPLADFAQGWGPISYA NGSGPDQRPYCWHYPPRPCGIVPAKSVCGPVYCFTPSPWVGTTDRSGAPTY NWGENDTDVFVLNNTRPPLGNWFGCTWMNSTGFTKVCGAPPCVIGGVGNNT LHCPTDCFRKHPEATYSRCGSGPWITPRCLVHYPYRLWHYPCTVNYTLFKVRM YVGGVEHRLEAACNWTRGERCDLDDRDRSELSPLLLSTTQWQVLPCSFTTLP ALTTGLIHLHQGIVDVQYLYGVGSSIASWAIKWEYVVLLFLLLADARVCSCLWM MLLISQVEAALENLWLNAASLAGTHGLVSFLVFFCFAWYLKGRWVPGAAYALY GMWPLLLLLLALPQRAYALDTEVAASCGGWLVGLMALTLSPYYKRYISWCLW WLQYFLTRVEAQLHVWVPPLNVRGGRDAVILLMCWHPTLVFDITKLLLAVFGP LWILQASLLKVPYFVRVQGLLRICALARKMAGGHYVQMAIIKLGALTGTYVYNHL TPLRDWAHNGLRDLAVAVEPWFSQMETKLITWGADTAACGDIINGLPVSARR GQEILLGPADGMVSKGWRLLAPITAYTQQTRGLLGCIITSLTGRDKNQVEGEVQI VSTAAQTFLATCINGVCWTVYHGAGTRTIASPKGPVIQMYTNVDKDLVGWPAP QGARSLTPCACGSSDLYLITRQADVIPARRRGDSRAALLSPRPISTLKGSSGGP LLCPAGHAVGIFRAAVCTRGVAKAVDFIPVENLETTMRSPVYTDNSSPPAVPQS FQVAHLHAPTGSGKSTKVPAAYASQGYKVLVLNPSVAATLSFGAYMSKAHGID PNIRTGVRTITTGSPITYSTYGKFLADGGCSAGAYDIIICDECHSTDATSILGIGTV LDQAETAGARLVVLAAATPPGSVTVPHSNIEEVALSTTGEIPFYGKAIPLEVIKGG RHLIFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPASGDVVVVATDALMTG YTGDFDSVIDCNTSVIQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKPGI YRFVAPGERPSGMFDSSILCECYDAGCAWYELTPAETTVRLRAYMNTPGLPVC QDHLEFWEGVFTGLTRIDAHFLSQTKQSGENLPYLVAYQATVCARARAPPPSW DSMWKCLIRLKPMLTGPTPLLYRLGAVQNEITLTHPVTKYIMTCMAADLEVVTST VVVMVGGLLAALAAYCLSTGCVVIVGRIVLSGKPAIIPDREVLYREFDEMEECSQ HLPYIEQGMMLAEQFKQKALGLLQTASRQAEVIAPAVQTNWQKLEAFWAKHM WNFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTSQTLLFNILGGVVVAAQL AAPGAATAFVGAGLAGAAIGSVGLGKVLVDILTGYGAGVAGALVAFKIMSGEVP STEDLVNLLPAILSPGALVVGVICAGILRRHVGPGEGAVQWMNRLIAFASRGNH VSPAHYVPESDAAARVTAILSSLTVTQLLRRLHQWISSECTTPCSGSWLRDIWD WICEVLSDFKTWLKAKLMPQLPGIPFVSCQRGYRGVWRGDGIMHTRCHCGAEI TGHVKNGTMRIVGPRTCRNMWSGTFPINAYTTGPCTPLPAPNYTFALWRVSAE EYVEIRQVGDFHYVTGMTTDNLKCPCQVPSPEFFTELDGVRLHRFAPPCKPLL REEVSFRVGLHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAGRRLARGS PPSVASSSASQLSAPSLKATCTANHDSPDAELIEANLLWRQEVGGNITRVESEN KVIVLDSFDPLVAEEDEREISVPAEILRKSRRFAPALPIWARPDYNPPLLETWKK PDYEPPWHGCPLPPPQSPPVPPPRKKRTWLTESTVSTALAELATKSFGSSST SGITGDNTTTSSEPAPSGCPPDSDAESYSSMPPLEGEPGDPDLSDGSWSTVS SEAGTEDVVCCSMSYSWTGALVTPCAAEEQKLPINALSNSLLRHHNLVYSTTS RSACQRQKKVTFDRLQVLDSHYQDVLKEVKAAASKVKANLLSVEEACSLTPPH SARSKFGYGAKDVRCHARKAVNHINSVWKDLLEDSVTPIDTTIMAKNEVFCVDP AKGGRKPARLIVFPDLGVRVCEKMALYDVVSKLPLAVMGSSYGFQYSPGQRVE FLVQAWKSKKTPMGFSYDTRCFDSTVTESDIRTEEAIYQCCDLDPQARVAIKSL TERLYVGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKARAACRAAGLQ DCTMLVCGDDLVVIAESDGVEEDNRALRAFTEAMTRYSAPPGDPPQPEYDLELI TSCSSNVSVAHDGAGKRVYYLTRDPTTPLARAAWETARHTPINSWLGNIIMFAP TLWARMILMTHFFSVLIARDQLEQALDCEIYGACYSIEPLDLPPIIQRLHGLSAFS LHGYSPVELNRVGACLRKLGVPPLRAWRHRARNVRARLLSRGGRAAICGKYLF NWAVRTKLKLTPIAAAGQLDLSGWFTAGYSGGDIYHSVSHARPRWFWFCLLLL AAGVGIYLLPNR

Design35-mosaic1-serial Amino Acid Sequence SEQ ID NO: 54 MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRG SRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGV RVLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSTGLYHVTNDCPN SSIVYEAADAILHTPGCVPCVREGNASRCVVVALTPTLAARNSSIPTTTIRRHVDL LVGAAAFCSAMYVGDLCGSVFLVSQLFTFSPRRHWTTQDCNCSIYPGHITGHR MAWDMMMNWSPTTALVVSQLLRIPQAVVDMVAGAHWGVLAGLAYYSMVGN WAKVLWLLLFAGVDAETRVTGGAAGHTAFGFASFLAPGAKQKIQLINTNGSW HINRTALNCNDSLNTGFLAALFYVHKFNSSGCPERLASCRPLADFDQGWGPISY ANGSGPDQRPYCWHYAPRPCGIVPASQVCGPVYCFTPSPWVGTTDRFGVPT YSWGENETDVLLLNNTRPPQGNWFGCTWMNSTGFTKTCGGPPCNIGGVGNN TLTCPTDCFRKHPEATYTKCGSGPWLTPRCLVDYPYRLWHYPCTVNFTIFKVR MYVGGVEHRLEAACNWTRGERCDLEDRDRSELSPLLLSTTQWQVLPCSFTTL PALSTGLIHLHQNIVDVQYLYGVGSSIASWAIKWEYVVLLFLLLADARVCACLWM MLLIAQAEAALENLVVLNAASVAGAHGILSFLVFFCAAVVYIKGRLVPGAAYALYG VWPLLLLLLALPPRAYAMDREMAASCGGWLVGLMALTLSPYYKRYISWCLWW LQYFLTRVEAQLHVVVVPPLNVRGGRDAIILLTCVVHPTLVFDITKLLLAVFGPLWI LQASLLKVPYFVRAQGLIRACMLVRKVAGGHYVQMAIIKLGALTGTYVYNHLTPL RDWAHNGLRDLAVAVEPVVFSDMETKIITWGADTAACGDIINGLPVSARRGREI LLGPADGMVSKGWRLLAPITAYAQQTRGLLGCIITSLTGRDKNQVEGEVQVVST ATQSFLATCINGVCWTVYHGAGTRTIASPKGPVIQMYTNVDQDLVGWPAPQGA RSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPLLC PAGHAVGIFRAAVCTRGVAKAVDFIPVESMETTMRSPVFTDNSSPPAVPQTFQ VAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNI RTGVRTITTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGTVLD QAETAGARLVVLATATPPGSVTVPHPNIEEVALSTTGEIPFYGKAIPLEVIKGGR HLIFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVATDALMTGY TGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGKPGI YRFVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETTVRLRAYLNTPGLPVC QDHLEFWEGVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARAQAPPPS WDQMWKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMTCMSADLEVVT STVVVLVGGVLAALAAYCLTTGSVVIVGRIVLSGKPAIIPDREVLYREFDEMEECA SHLPYIEQGMQLAEQFKQKALGLLQTATKQAEAAAPVVESKWRALEAFWAKH MWNFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTSQTLLFNILGGWVAAQ LAPPSAASAFVGAGIAGAAVGSIGLGKVLVDILAGYGAGVAGALVAFKIMSGEVP STEDLVNLLPAILSPGALWGVVCAAILRRHVGPGEGAVQWMNRLIAFASRGNH VSPTHYVPESDAAARVTQILSSLTITQLLKRLHQWINEDCSTPCSGSWLRDVWD WICTVLTDFKTWLQSKLLPRLPGVPFFSCQRGYKGVWRGDGIMHTRCHCGAEI TGHVKNGSMRIVGPKTCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAAE EYVEVTRVGDFHYVTGMTTDNLKCPCQVPSPEFFTELDGVRLHRFAPPCKPLL REEVSFRVGLHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAETAKRRLARGSP PSLASSSASQLSAPSLKATCTTHHDSPDADLIEANLLWRQEMGGNITRVESENK WILDSFDPLVAEEDEREISVPAEILRKSRRFAPALPIWARPDYNPPLLESWKDP DYVPPVVHGCPLPPTKAPPIPPPRRKRTVVLTESTVSSALAELATKSFGSSSTS GITGDNTTTSSEPAPSGCPPDSDAESYSSMPPLEGEPGDPDLSDGSWSTVSE EASEDVVCCSMSYTWTGALITPCAAEESKLPINALSNSLLRHHNMVYATTSRSA SQRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSVEEACSLTPPHSAK SKFGYGAKDVRCHARKAVNHINSVWKDLLEDSVTPIDTTIMAKNEVFCVQPEKG GRKPARLIVFPDLGVRVCEKMALYDWSTLPQAVMGSSYGFQYSPGQRVEFLV QAWKSKKTPMGFSYDTRCFDSTVTESDIRTEEAIYQCCDLDPQARVAIKSLTER LYVGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKASAACRAAKLQDC TMLVCGDDLVVICESAGTQEDAASLRAFTEAMTRYSAPPGDPPQPEYDLELITS CSSNVSVAHDASGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMYAPT LWARMILMTHFFSILLAQEQLEKALDCQIYGACYSIEPLDLPPIIQRLHGLSAFSL HSYSPGEINRVAACLRKLGVPPLRAWRHRARSVRAKLLSQGGRAATCGKYLFN WAVRTKLKLTPIPAASQLDLSGWFVAGYSGGDIYHSLSRARPRWFMLCLLLLSV GVGIYLLPNR*

Design35-mosaic2-serial Amino Acid Sequence SEQ ID NO: 55 MSTLPKPQRKTKRNTNRRPMDVKFPGGGQIAGGVYLLPRRGPRLGVRAVRKT SERSQPRGRRQPIPKARQPQGRHWAQPGYPWPLYGNEGCGWPGWLLSPRG SRPHWGPNDPRRRSRNLGKVIDTITCGLADLMGYIPWGAPLGGVAAALAHGV RAIEDGINYATGNLPGCSFSIFILALLSCLTTPASALTYGNSSGLYHLTNDCPNSS IVLEADAMILHLPGCLPCVRVDNRSTCWHAVSPTLAIPNASTPATGFRRHVDLLA GAAWCSSLYIGDLCGSLFLAGQLFTFQPRRHWTVQDCNCSIYTGHVTGHRMA WDMMMNWSPTTTLVLSSILRVPEICASVIFGGHWGILLAVAYFGMAGNWLKVL AVLFLFAGVEATTTTGHAVGRTTGGLVSIFSPGAKQNLQLINTNGSWHINRTAL NCNDSLQTGFIASLFYTHKFNSSGCPERMAACKPLADFRQGWGQITYKVNISG PSDDRPYCWHYAPRPCDWPARTVCGPVYCFTPSPVWGTTDRRGNPTYTW GENETDVFMLESLRPPTGGWFGCTWMNSTGFTKTCGAPPCQIVPGDYNSSAN ELLCPTDCFRKHPEATYQRCGSGPWVTPRCLVDYPYRLWHYPCTVNFTLHKV RMFVGGIEHRFDAACNWTRGERCELHDRDRIEMSPLLFSTTQLAILPCSFSTMP ALSTGLIHLHQNVVDVQYLYGVSSSVTSVVVVKWEYIVLMFLVLADARICTCLWL MLLISNVEAAVERLVVLNAASAAGTAGWWWAVLFLCCVVVYVKGRLVPACTYM ALGMWPLLLTILALPPRAYAMDNEQAASLGAVGLLVITIFTITPMYKKLLTCFIWW NQYFLARAEAMVHEVVVPDLRVRGGRDSIILLTCLLHPQLGFEVTKILLAILAPLYI LQYSLLKVPYFVRAHILLRACLLVRRLAGGKYVQACLLRLGAWTGTFVYDHLAP LSDWASDGLRDLAVAVEPVIFSPMEKKVITWGADTAACGDILSGLPVSARLGNL VLLGPADDMQRGGWKLLAPITAYAQQTRGLVGTIVTSLTGRDKNEVEGEIQVVS TATQSFLATSINGVMWTVYHGAGSKTLAGPKGPVCQMYTNVDKDLVGWPSPP GARSLTPCACGSSDLYLVTREADVIPARRRGDNRAALLSPRPISTLKGSSGGPI MCPSGHVVGLFRAAVCTRGVAKSLDFIPVENMETTMRSPSFTDNSTPPAVPQT YQVGYLHAPTGSGKSTRVPAAYASQGYKVLVLNPSVAATLSFGSYMRQAYGV EPNVRTGVRTVTTGGAITYSTYGKFLADGGCSGGAYDVIICDECHSTDPTTVLGI GTVLDQAETAGVRLTVLATATPPGSITVPHPNITETALPTTGEIPFYGKAIPLEYIK GGRHLIFCHSKKKCDELAGKLKSLGLNAVAFYRGVDVSVIPTSGDVVVCATDAL MTGYTGDFDSVIDCNVAVTQVVDFSLDPTFSIETTTVPQDAVARSQRRGRTGR GKPGVYRFVSQGERPSGMFDTVVLCEAYDTGCAVVYELTPSETTVRLRAYMNT PGLPVCQDHLEFWEAVFTGLTHIDAHFLSQTKQGGENFAYLVAYQATVCARAK APPPSWDTMWKCLIRLKPTLTGPTPLLYRLGAVQNEIITTHPITKYIMTCMSADL EVITSTVVVLVGGVVAALAAYCLSVGCVVICGRITLTGKPAVVPDREILYQQFDEM EECSRHIPYLAEGQQIAEQFRQKVLGLLQASAKQAEELKPAVHSAWPKLEQFW QKHLWNFVSGIQYLAGLSTLPGNPAVASLMSFSASLTSPLSTSTTLLLNILGGW VASQLANPTASTAFVVSGLAGAAVGSIGLGRVLVDVLAGYGAGVSGALVAFKIM SGECPTTEDMVNLLPALLSPGALWGWCAAILRRHVGPAEGANQWMNRLIAF ASRGNHVSPTHYVPETDASKNVTQILTSLTITSLLRRLHQVVVNEDTATPCATSW LRDVWDVVVCTVLSDFKVWLQAKLLPRLPGIPFLSCQTGYRGVWAGDGVCHTT CTCGAVIAGHVKNGTMKITGPKTCSNTWHGTFPINATTTGPSTPRPAPNYQRAL WRVSAEDYVEVRRLGDCHYVVGVTAEGLKCPCQVPAPEFFTEVDGVRIHRYA PPCKPLLRDEVTFSVGLSNYAIGSQLPCEPEPDVTVVTSMLTDPTHITAETAARR LKRGSPPSLASSSASQLSAPSLKATCTTSKDHPDMELIEANLLWRQEMGSNITR VESENKVVVLDSFEPLTAEYDEREISVSAECHRPPRHKFPPALPIWARPDYNPP LLQAWQMPGYEPPVVSGCAVAPPKPAPIPPPRRKRLVHLDESTVSHALAQLAD KVFVESSNDPGPSSDSGLSITSPVPPAPSTPDDACSEAESYSSMPPLEGEPGD PDLSSGSWSTVSDQDDWCCSMSYSWTGALITPCAAEEEKLPINPLSNSLIRHH NMVYSTTSRSASLRQKKVTFDRVQVFDQHYQDVLKEIKLRASTVQAKLLSIEEA CDLTPSHSARSKYGYGAQDVRSHASKAINHINSVWEDLLEDSDTPIPTTIMAKN EVFCVDPSKGGRKPARLIVYPDLGVRVCEKMALYDVTRKLPQAVMGSAYGFQY SPNQRVEYLLKMWRSKKVPMGFSYDTRCFDSTVTERDIRTENDIYQSCQLDPV ARKAVSSLTERLYVGGPMVNSKGQSCGYRRCRASGVLPTSMGNTLTCYLKAQ AACRAANIKDCDMLVCGDDLVVICESAGVQEDTASLRAFTDAMTRYSAPPGDA PQPTYDLELITSCSSNVSVAHDGNGKRYYYLTRDCTTPLARAAWETARHTPVN SWLGNIIMFAPTIWVRMVLMTHFFSILQSQEQLEKALDFDIYGVTYSVSPLDLPAI IQRLHGMAAFSLHGYSPGELNRVGACLRKLGAPPLRAWRHRARAVRAKLIAQG GKAAICGKYLFNWAVKTKLKLTPLVSASKLDLSGWFVAGYDGGDIYHSVSQAR PRLLLLGLLLLTVGVGIFLLPAR

Design35-mosaic3-serial Amino Acid Sequence SEQ ID NO: 56 MSTNPKPQRITKRNINRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRTTRKTS ERSQPRGRRQPIPKDRRSTGKSWGKPGYPWPLYGNEGLGWAGWLLSPRGS RPTWGPTDPRHRSRNLGRVIDTITCGFADLMGYIPVVGAPVGGVARALAHGVR VLEDGINYATGNLPGCSFSIFLLALLSCVTVPVSAVEVRNISSSYYATNDCSNNSI TWQLTNAVLHLPGCVPCENDNGTLRCWIQVTPNVAVKHRGALTHNLRTHVDMI VMAATVCSALYVGDVCGAVMIVSQALIVSPERHNFTQECNCSIYPGTITGHRMA WDMMLNWSPTLTMILAYAARVPELVLEVVFGGHWGVMFGLAYFSMQGAWAK VIAILLLVAGVDATTYSTGAQAGRGASGIANLFTPGAKQNIQLINTNGSWHINRTA LNCNDSLKTGFIASLFYTHRFNSSGCPERLSSCRGLDDFRIGWGTLEYETNVTN DEDMRPYCWHYPPKPCGIVSARTVCGPVYCFTPSPWVGTTDRQGVPTYSWG ENETDVFLLNSTRPPRGAWFGCTWMNGTGFTKTCGAPPCRIRRDYNSTLDLL CPTDCFRKHPDATYLKCGAGPWLTPKCLVEYPYRLWHYPCTINYTIFKIRMYVG GVEHRLSAACNFTRGDRCRLEDRDRGQQSPLLHSTTEWAVLPCSFSDLPALST GLLHLHQNIVDVQYMYGLSPALTKYIVRWEVVVVLLFLLLADARVCACLWMLIILG QAEAALEKLIILHSASAASANGPLWFFIFFTAAWYLKGRVVPVATYSVLGLWSFL LLVLALPQQAYALDAAEQGELGLVILVIISIFTLTPAYKILLSRSVWWLSYMLVLAE AQIQQVVVPPLEARGGRDGIIWVAVILHPRLVFEVTKWLLAILGSAYLLKASLLRV PYFVRAHALLRVCTLVRHLAGARYIQMLLITIGRWTGTYIYDHLSPLSTWAAQGL RDLAVAVEPIIFSPMEKKVIVWGAETVACGDILHGLPVSARLGREVLLGPADGYT SKGWKLLAPITAYTQQTRGLLGAIVVSMTGRDKTEQAGEIQVLSTVTQSFLGTSI SGVLWTVYHGAGNKTLAGSRGPVTQMYSSAEGDLVGWPSPPGTKSLDPCTC GAVDLYLVTRNADVIPVRRKDDRRGALLSPRPLSTLKGSSGGPVLCPRGHAVG LFRAAVCSRGVAKSIDFIPVETLDIVTRSPTFSDNSTPPAVPQSYQVGYLHAPTG SGKSTKVPVAYAAQGYKVLVLNPSVAATLGFGAYLSKAHGINPNIRTGVRTVTT GDPITYSTYGKFIADGGCSAGAYDIIICDECHSVDATTILGIGTVLDQAETAGVRL VVLATATPPGTVTTPHSNIEEVALGHEGEIPFYGRAIPLSYIKGGRHLIFCHSRKK CDELAAALRGMGLNAVAYYRGLDVSVIPTQGDWWATDALMTGFTGDFDTVI DCNVAVTQIVDFSLDPTFTITTQTVPQDAVSRSQRRGRTGRGRLGIYRYVSTGE RASGMFDSWLCECYDAGAAWYELTPAETTVRLRAYFNTPGLPVCQDHLEFW EAVFTGLTHIDAHFLSQTKQSGENFAYLTAYQATVCARAKAPPPSWDVMWKCL TRLKPTLVGPTPLLYRLGSVTNEVTLTHPVTKYIATCMQADLEVMTSTWVLAGG VLAAVAAYCLATGCVSIIGRLHINQRAVVAPDKEVLYEAFDEMEECASKAALIEE GQRIAEMLKSKIQGLLQQASKQAQDIQPAVQASWPKVEQFWAKHMWNFHSGI PYLARLSQLPGNPAVASMMAFSAALTSPLSTSTTILLNIMGGWLASQIAPPAGAT GFVVSGLVGAAVGSIGLGKILVDVLAGYGAGISGALVAFKIMSGEKPSVEDVVNL LPGILSPGALWGVICAAILRRHVGQGEGAVQWMNRLIAFASRGNHVAPTHYVT ESDASQRVTQLLGSLTITSLLRRLHNWITEDCPIPCAGSWLRDVWDVVVCTILTD FKNWLTSKLFPKMPGLPFISCQKGYRGVWAGTGIMTTRCPCGANISGNVRLGS MRITGPKTCMNTWQGTFPINCYTEGPCVPKPPPNYKTAIWRVAASEYVEVTQH GSFSYVTGLTSDNLKVPCQLPSPEFFSWVDGVQIHRFAPTPKPFFRDEVSFCV GLNSFWGSQLPCDPEPDTEVLASMLTDPSHITAEAAARRLARGSPPSEASSSA SQLSAPSLRATCTTHGKTYDVDMVDANLFMGGDVTRIESESKVWLDSLDSMT EVEDDREPSVPSEYLIRRRKFPPALPPWARPDYNPPVIETWKRPGYEPPTVLG CALPPTPQAPVPPPRRRRAKVLTQDNVEGVLREMADKVLSPLQDHNDSGHST GADTGGDSVQQPSDETAASETGSLSSMPPLEGEPGDPDLEFEPARSAPPSEG ECEVIDSDSKSWSTVSDQEDSVICCSMSYSWTGALITPCGPEEEKLPINPLSNS LLRYHNKVYCTTSKSASLRAKKVTFDRVQVLDAHYDSVLKDIKLAASKVSARLLT LEEACQLTPPHSARSKYGFGAKEVRSLSGRAVNHIKSVWKDLLEDSQTPIPTTI MAKNEVFCVDPTKGGKKAARLIVYPDLSVRVCEKMALYDVTQKLPQAVMGASY GFQYSPAQRVEFLLKAWAEKKDPMGFSYDTRCFDSTVTERDIRTEESIYQACS LPQEARTVIHSLTERLYVGGPMFNSKGQTCGYRRCRASGVFTTSMGNTMTCYI KALAACKAAGIVAPTMLVCGDDLVVISESQGNEEDERNLRAFTEAMTRYSAPP GDLPRPEYDLELITSCSSNVSVALDSRGRRRYFLTRDPTTPITRAAWETVRHSP VNSWLGNIIQYAPTIWVRMVIMTHFFSILLAQDTLNQNLNFEMYGAVYSVNPLDL PAIIERLHGLDAFSLHTYSPHELSRVAATLRKLGAPPLRAWKSRARAVRASLIAQ GGRAAICGRYLFNWAVKTKLKLTPLPEARLLDLSSWFTVGAGGGDIYHSVSRA RPRLLLLCLLLLSVGVGIFLLPAR

Design35-mosaic4-serial Amino Acid Sequence SEQ ID NO: 57 MSTNPKPQRKTQRNTNRRPTDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKT SERSQPRGRRQPIPKARRSEGRSWAQPGYPWPLYGNEGCGWAGWLLSPRG SRPSWGPNDPRGRSRNLGKVIDTLTCGFADLMGYIPLVGAPVGSVARALAHGV RAVEDGINYATGNLPGCSFSIFLLALLSCLTVPASAINYRNTSGIYHVTNDCPNS SIVYEADHHILHLPGCVPCVREGNQSRCVVVALTPTVAAPYIGAPLESLRSHVDL MVGAATVCSALYIGDLCGGLFLAGQMFSFRPRRHWTTQECNCSIYTGHITGHR MAWDMMMSWSPTTTLVLSQVMRIPSTLVDLLAGGHWGVLVGVAYFSMQANW AKVILVLFLFAGVDAETHVSGAAVGRSTAGLANLFSSGSKQNLQLINSNGSWHI NRTSLNCNDSLNTGFLASLFYTHKFNSSGCSERLACCKSLDSYGQGWGPLGV ANISGPSEDRPYCWHYPPRPCGIVPALSVCGPVYCFTPSPIVVGTTDRLGVPTY TWGENESDVFLLNSTRPPQGAWFGCVWMNSTGFTKACGAPPCEVNTNNGTW HCPTDCFRKHPETTYAKCGSGPWITPRCLIHYPYRLWHFPCTVNFTVFKVRTFI GGIEHRMEAACNWTRGEVCGLEHRDRAELSPLLLSTTTWQILPCSFTTLPALST GLIHLHQNTVDVQYLYGVGSAVVSWALKWEYVVLAFLLLADARVSACLWMMF MVSQVEAALSNLININAASAAGNHGFVVYAIFFICIAWHVKGRLPAAATYVACGM WPLLLLLLMLPERAYAFDREVAGSLGGAVVVALTILTLSPHYKSWLAKGLWWIQ YFIARAEALLHVYVPSFDVRGPRDSLIILAVLACPHLTFDITKHLLAILGPLYILQAS LLRIPYFVRAHALIKICSLLRGVVHGKYCQMVVLKMGALTGTYIYDHLTPLSDWA AEGLRDLAVALEPVVFTAMEKKVIVWGADTAACGDIIRGLPVSARLGNEILLGPA DSETSKGWRLLAPITAYAQQTRGLFSTIITSLTGRDTNENCGEVQVLSTATQSFL GTAVNGVMWSVYHGAGSKTISGPKGPVNQMYTNVDQDLVGWPAPPGVKSLT PCTCGASDLYLVTRHADWPVRRRGDTRGALLSPRPISILKGSSGGPLLCPMG HAAGLFRAAVCTRGVAKAVDFVPVESLETTMRSPVFTDNSTPPAVPQTYQVAH LHAPTGSGKSTKVPAAHAAQGYKVLVLNPSVAATLGFGAYMSKAYGIDPNIRSG VRTITTGAPITYSTYGKFLADGGCAGGAYDIIICDECHSTDSTTILGIGTVLDQAET AGVRLTVLATATPPGSVTTPHSNIEEVALPTTGEVPFYGKAIPLELIKGGRHLIFC HSKKKCDELAKQLTSLGLNAVAYYRGLDVSVIPLSGDVWCATDALMTGFTGDF DSVIDCNTSVIQTVDFSLDPTFSIEITTVPQDAVSRSQRRGRTGRGRLGIYRYVT PGERPSGIFDTSVICECYDAGCAWYELTPAETTTRLRAYFNTPGLPVCQDHLEF WESVFTGLTQIDGHFLSQTKQSGENFPYLVAYQATVCARALAPPPSWDTMWK CLLRLKPTLRGPTPLLYRLGSVQNEVTLTHPITKYIMACMSADLEVVTSTVVVMV GGLLAALAAYCLSVGSVVIVGRVVLSGQPAVIPDREVLYQQFDEMEECSKHLPL VEHGLQLAEQFKQKAVGLLNFAGKQAQEATPVIQSNFAKLEQFWAKHMWNFIS GIQYLAGLSTLPGNPAIASLMSFTAAVTSPLTTQQTLLFNILGGVVVASQIATPTAS TAFVISGIAGAAVGSVGLGKILVDILAGYGAGVAGAVVTFKIMSGEMPSTEDLVN LLPAILSPGALVVEVVCPAILRRHVGPGEGAVQWMNRLIAFASRGNHVAPTHYV PESDAARRVTTILSSLTVTSLLRRLHKWINEDCSTPCAESWLWEVWDWVCTVL SDFKTWLKAKLLPLMPGIPFLSCQRGYRGEWRGDGVMHTTCPCGAELAGHIK NGSMRITGPKTCSNTWHGTFPINAYTTGPGVPVPAPNYKFALWRVSAEEYVEV RRVGDFHYVTGVTQDNIKCPCQVPAPEFFTEVDGIRLHRHAPKCKPLLRDEVSF SVGLNSFWGSQLPCEPEPDVAVLTSMLTDPSHITAESARRRLARGSRPSLASS SASQLSPRLLQATCTAPHDSPGTDLLEANLLWGSTATRVETDEKVIILDSFEPRV AESDDDREVSVAAEILRPTKKFPPALPIWARPDYNPPLTETWKQQDYKPPTVH GCALPPSKQPPVPPPRRKRTVQLTESWSTALAELAAKTFGQSELGSDSGADL TTPTETTDSGPILVDDASDDGSYSSMPPLEGEPGDPDLTSDSWSTVSGSEDVV CCSMSYSWTGALVTPCAAEESKLPISPLSNSLLRHHNMVYATTTRSAVTRQKK VTFDRLQVVDNHYNETLKEIKARASRVKARLLTTEEACDLTPPHSARSKFGYGA KDVRSHSRKAINHINSVWEDLLEDNNTPIPTTIMAKNEVFAVNPAKGGRKPARLI VYPDLGVRVCEKRALHDVINQLPKAVMGAAYGFQYSPAQRVEFLLTSWKSKKT PMGFSYDTRCFDSTVTEKDIRTEEEVYQCCDLEPEARKVIAALTERLYVGGPMH NSKGDLCGYRRCRASGVYTTSFGNTLTCYLKATAAIKAAGLRDCTMLVCGDDL WIAESDGVEEDNRALRAFTEAMTRYSAPPGDAPQPAYDLELITSCSSNVSVAH DATGKKVYYLTRDPETPLARAAWETVRHTPVNSWLGNIIVYAPTIVVVRMILMTH FFSILQSQEALEKALDFDMYGVTYSITPLDLPAIIQRLHGLSAFTLHGYSPHELNR VAGSLRKLGVPPLRAWRHRARAVRAKLIAQGGRAKICGIYLFNWAVKTKLKLTP LPAAAKLDLSGWFTVGAGGGDIYHSMSHARPRYLLLCLLLLSVGVGIFLLPAR

Design35-mosaic5-serial Amino Acid Sequence SEQ ID NO: 58 MSTLPKPKRQTKRNTLRRPKNVKFPAGGQIVGEVYVLPRRGPKLGVRATRKNS ERSQPRGRRQPIPKARRPTGRSWGQPGYPWPLYANEGLGWAGWLLSPRSSR PNWGPNDPRRKSPNLGRVIHTLTCGFPHLMGYIPLVGGPVGGVARALAHGVR ALEDGINFATGNLPGCSFSIFLLALFSCLIHPAASLEWRNTSGLYVLTNDCSNSSI VYEADDVILHTPGCVPCVQDGNTSTCWTPVTPTVAVRYVGATTASIRSHVDLLV GAATMCSALYVGDMCGAVFLVGQAFTFRPRRHQTVQTCNCSLYPGHLSGHR MAWDMMMKWSPTTALLMAQLLRIPQVVIDIIAGAHWGILAGLAYYSMQGNWAK VAIIMVMFSGVDAHTYTTGGTASRHTQAFAGLFDIGPQQKLQLVNTNGSWHINS TALNCNESINTGFIAGLFYYHKFNSTGCPQRLSSCKPITFFKQGWGPLTDANITG PSDDKPYCWHYPPRPCNITKPLNVCGPVYCFTPSPVWGTTDIKGLPTYRFGV NESDVFLLTSLRPPQGRWFGCVWMNSTGFVKTCGAPPCNIYGGMKDIEANQT HLKCPTDCFRKHPEATYSRCGAGPWLTPRCMVDYPYRLWHYPCTVNFTLFKV RMFVGGFEHRFTAACNWTRGERCDIEDRDRSEQHPLLHSTTELAILPCSFTPM PALSTGLIHLHQNIVDTQYLYGLSSSIVSWAVKWEYIMLVFLLLADARVCVALWL MLMISQAEAALENLVTLNAVAAAGTHGIGVVYLVAFCAAWYVRGKLVPLVTYSLT GLWSLALLVLLLPQRAYAWSGEDSATLGAGVLVLFGFFTLSPWYKHWIGRLIW WNQYTICRCESALQVWVPPLLARGSRDGVILLTSLLYPSLIFDITKLLIAVLGPLYL IQAALTSTPYFVRAHVLVRLCMLVRSVMGGKYFQMIILSIGRWFNTYLYDHLAP MQHWAAAGLKDLAVATEPVIFSPMEIKVITWGADTAACGDILCGLPVSARLGRE LLLGPADDYREMGWRLLAPITAHAQQTRGLFGTIVTSLTGRDKNWTGEVQVLS TATQTFLGTTVGGVMWTVYHGAGSRTLAGAKHPALQMYTNVDQDLVGWPAP PGAKSLEPCACGSADLYLVTRDADVIPARRRGDSTASLLSPRPLACLKGSSGG PVMCPSGHVAGIFRAAVCTRGVAKALQFIPVETLSTQARSPSFSDNSTPPAVPH EFQVGHLHAPTGSGKSTKVPAAYVAQGYNVLVLNPSVAATLGFGSFMSRAYGI DPNIRTGNRTVTTGAKLTYSTYGKFFADGGCSGGAYDVIICDECHAQDATSILGI GTVLDQAETAGVRLTVLATRTPPGSITVPHSNIEEVALGSEGEIPFYGKAIPIALL KGGRHLIFCHSKKKCDEIASKLRGMGLNAVAYYRGLDVAVIPATGDVWCSTDA LMTGFTGDFDSVIDCNVAVEQYVDFSLDPTFSIETRTAPQDAVSRSQRRGRTG RGRHGIYRYVSSGERPSGIFDSVVLCECYDAGCSVVYDLQPAETTVRLRAYLST PGLPVCQDHLDFWESVFTGLTHIDAHFLSQTKQQGLNFSYLTAYQATVCARAK ASPPCWDEMWKCLVRLKPTLHGPTPLLYRLGPVQNETCLTHPITKYVMACMSA DLEVTTSTWVLLGGVLAALAAYCLSVGCVVIVGHIELGGKPALVPDKEVLYQQY DEMEECSQAAPYIEQAQAIAHQFKEKVLGLLQRATQQQAVIEPIVATNWQKLEA FWHKHMWNFVSGIQYLAGLPTLPGNPAVASLMAFTASVTSPLTTNQTMFFNIL GGVVVATHLAGPQSSSAFVVSGLAGAAIGGIGLGRVLLDILAGYGAGVSGALVAF KIMCGERPTAEELVNLLPSILCPGALVVGVICAAVLRRHIGPGEGAVQWMNRLIA FASRGNHGSPTHYVPESDAAAKVTALLSSLTVTRLLRRLHQWINEDYPSPCSD DWLRIIWDVVVCSVLADFKTWLSAKIMPALPGLPFISCQKGYKGVWRGDGVMST RCPCGATITGHVKNGSMRLAGPRTCANMWHGTFPINEYTTGPSTPCPSPNYT RALWRVAANSYVEVRRVGDFHYITGATEDELKCPCQVPAAEFFTEVDGVRLHR YAPPCKPLLRDDITFMVGLNSYAIGSQLPCEPEPDVTVLTSMLSDPAHITAETAK RRLNRGSPPSLANSSASQLSAPSLKATCQTHRPHPDAELVDANLLWRQEMGS NITRVESETKWILDSFEPLRAETDDAELSVAAECFKKPPKYPPALPIWARPDYN PPLLDRWKAPDYVPPTVHGCALPPRGAPPVPPPRRKRTIQLDGSNVSAALAAL AEKSFPSSKPQEENSSSSGVDTQSSTTSKVPPSPGGESDSESCSSMPPLEGE PGDPDLSCDSWSTVSDSEEQSWCCSMSYSWTGALITPCSAEEEKLPISPLSN SLLRHHNLVYSTSSRSASQRQRKVTFDRLQVLDDHYKTALKEVKERASRVKAR MLTIEEACALVPPHSARSKFGYSAKDVRSLSSRAINQIRSVWEDLLEDTTTPIPT TIMAKNEVFAVEPSKGGKKPARLIVYPDLGVRVCEKRALYDVIQKLSIATMGPAY GFQYSPQQRVERLLKMWTSKKTPLGFSYDTRCFDSTVTEQDIRVEEEIYQCCN LEPEARKVISSLTERLYCGGPMYNSKGQQCGYRRCRASGVLPTSFGNTITCYIK ATAAAKAAGLRNPDFLVCGDDLVAICESQGTHEDEASLRAFTEAMTRYSAPPG DPPVPAYDLELVTSCSSNVSVARDDKGRRYYYLTRDATTPLARAAWETAKHSP VNSWLGNIIMYAPTIWVRMVMMTHFFSILQSQEILDRPLDFEMYGATYSVTPLDL PAIIERLHGLSAFTLHSYSPVELNRVAGTLRKLGCPPLRAWRHRARAGRAKLIA QGGKAKICGLYLFNWAVRTKTKLTPLPTAGQLDLSSWFTVGVGGNDIYHSVSR ARTRHLLLCLLLLTVGVGIFLLPAR

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What is claimed is:
 1. A multivalent HCV mosaic polypeptide composition comprising a set of polypeptides selected from the group consisting of the polypeptides of SEQ ID NOS: 42-44 and the polypeptides of SEQ ID NOS: 45-48.
 2. The composition according to claim 1, wherein one or more of the selected polypeptides are fragmented to present individual HCV proteins.
 3. The composition according claim 1, further comprising a pharmaceutically acceptable carrier.
 4. The composition according to claim 1, further comprising an adjuvant.
 5. The composition according to claim 1, further comprising a co-stimulatory molecule. 